DETAILED ACTION
This office action is in response to applicant’s filing dated July 15, 2026.
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 .
Status of Claims
Claims 1-14 and 16-30 are pending in the instant application. Acknowledgement is made of Applicant's remarks and amendments filed July 15, 2026. Acknowledgement is made of Applicant's addition of new claims 29 and 30. Claim 15 was previously canceled.
Applicants elected without traverse Group I, drawn to an aqueous topical suspension for treating or preventing an inflammatory or autoimmune disease or condition of human skin comprising 0.01 to 1% of one or more benzimidazole compounds, wherein at least some of the one or more benzimidazole compounds remain in undissolved form in the aqueous topical suspension; and 15 to 45% of an ethylene glycol based solvent; wherein the percentages are by weight of the aqueous topical suspension; and wherein the aqueous topical suspension does not include any aprotic solvents as the elected invention and a formulation comprising mebendazole, diethylene glycol monoethyl ether, and hydroxycellulose as the elected formulation species in the reply filed on June 1, 2026. The requirement is still deemed proper. Claims 4, 8-14 and 16-28 remain withdrawn.
New claims 29 and 30 read on the elected invention and thus are presently under examination.
Claims 1-3, 5-7, 29, and 30 are presently under examination as they relate to the elected species: mebendazole, diethylene glycol monoethyl ether, and hydroxycellulose
Priority
The present application is a CIP of US Application No. 18/212,065 filed on June 20, 2023, which claims benefit of US Provisional Application NO 63/353,907 filed on June 21, 2022. The present application claims benefit of US Provisional Application NOs. 63/635,923 and 63/650,567 filed on April 18, 2024 and May 22, 2024, respectively.
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) or under 35 U.S.C. 120 as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed applications, US Application No. 18/212,065 and US Provisional Applications 63/353,907; 63/635,923; and 63/650,567 fail to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. In a review of US Application No. 18/212,065 and US Provisional Applications 63/353,907; 63/635,923; and 63/650,567, disclosure of aprotic solvents was not identified. MPEP 2173.05(i) states:
Any negative limitation or exclusionary proviso must have basis in the original disclosure. If alternative elements are positively recited in the specification, they may be explicitly excluded in the claims. See In re Johnson, 558 F.2d 1008, 1019, 194 USPQ 187, 196 (CCPA 1977) ("[the] specification, having described the whole, necessarily described the part remaining."). In the instant case, the prior-filed applications do not appear to disclose aprotic solvents, thus the prior-filed applications do not provide sufficient support for the limitation “wherein the aqueous topical suspension does not include any aprotic solvents.”
The effective filing date of claims 1-3, 5-7, and 29 is April 16, 2025. The effective filing date of claim 30 is June 21, 2022.
Response to Arguments
Applicant argues:
The compositions as currently claimed, including the negative limitation related to aprotic solvents, are supported by at least the disclosure in Tables 10 and 17 of P2 and P3, which is identical to Tables 10 and 17 in CIP. These tables recite compositions including mebendazole, a viscosity modifying agent (such as hydroxycellulose), an ethylene glycol based solvent, and water in amounts that total 100%. No aprotic solvents are listed for these compositions, which supports the exclusion of aprotic solvents in the claims. Similarly, Parent, P2, P3, and CIP also all include several other tables for composition ingredients that total 100% and do not include aprotic solvents. These include Tables 2, 4, 8, and 9. Therefore, Parent, P2, and P3 all support the exclusion of aprotic solvents.
Examiner's response:
The above argument has been carefully considered and has not been found persuasive.
As set forth above, MPEP 2173.05(i) states: Any negative limitation or exclusionary proviso must have basis in the original disclosure. If alternative elements are positively recited in the specification, they may be explicitly excluded in the claims. See In re Johnson, 558 F.2d 1008, 1019, 194 USPQ 187, 196 (CCPA 1977) ("[the] specification, having described the whole, necessarily described the part remaining."). In the instant case, the prior-filed applications do not appear to disclose the term aprotic solvents generically, thus the prior-filed applications do not provide sufficient support for the limitation “wherein the aqueous topical suspension does not include any aprotic solvents.” Moreover, MPEP 2173.05(i) states: The mere absence of a positive recitation is not basis for an exclusion. There is no teaching or direction provided in the Parent (‘065), P2 (‘923), and P3 (‘567) that would direct anyone to exclude aprotic solvents. The Parent (‘065), P2 (‘923), and P3 (‘567) disclose solvents generically. The only mention of specific classes of solvents refers to ethylene and/or propylene glycol based solvents, sorbitol based solvents, and non-DMSO solvents. There is no mention of aprotic solvents and while DMSO is an aprotic solvent, a single aprotic solvent is insufficient to provide support for the scope encompassed by aprotic solvents, which includes any solvent lacks acidic hydrogens.
Applicant argues:
Additionally, several specific aprotic solvents (dimethylsulfoxide, methylsulfonylmethane, pyrrolidones, dimethylacetamide, laurocapram (Azone), isopropyl myristate, methyl nonanoate, and methyl caprate) are listed as possible ingredients for compositions in P1 (paragraph [0022]), Parent (paragraph [0034]), P2 (paragraph [0037]), and P3 (paragraph [0037]). A POSITA would understand that these are aprotic solvents. Each of P1 (paragraph [0022]), Parent (paragraph [0034]), P2 (paragraph [0037]), and P3 (paragraph [0037]) also explicitly state: "In other preferred embodiments, any of these ingredients may also be excluded from the composition or excluded from use in the methods of the invention." Therefore, a POSITA would understand that the inventors were in possession of a composition including the claims ingredients and excluding aprotic solvents as a subgenus of solvents based on the described exclusion of several species of aprotic solvents. See Ex parte Peterson, Appeal No. 2017-010881 at *3 (PTAB 2018) (finding disclosure of a sufficient number of species within a subgenus provides sufficient support for a claimed negative limitation excluding the subgenus).
Examiner's response:
The above argument has been carefully considered and has not been found persuasive.
The Examiner notes that dimethylsulfoxide, methylsulfonylmethane, pyrrolidones, dimethylacetamide, laurocapram (Azone), isopropyl myristate, methyl nonanoate, and methyl caprate) disclosed in P1 (‘907), Parent (‘065), P2 (‘923), and P3 (‘567) are not disclosed as solvents but as permeation enhancers, non-active excipients which may aid in or induce penetration of the active benzimidazole agent(s) into the facial skin or ocular tissue and substances that increase the flux of certain active agents through the skin or mucous membranes. While there is also disclosure of certain surfactants that may also increase penetration of active ingredients through solubilization, reduction in interfacial surface tension, or encapsulation of the active ingredient, none of the above listed excipients are listed as such. Thus, the fact that these agents may also function as aprotic solvents is not sufficient to provide written description support for aprotic solvents as these agents are not disclosed as solvents in the previously filed applications. Any negative limitation or exclusionary proviso must have basis in the original disclosure. In the instant case, there is no basis provided in the previously filed applications.
Applicant argues:
The explicit statement that in some embodiments "a solvent used in compositions herein does not include an aprotic solvent," such as in paragraph [0023] of CIP, is not included in P1, Parent, P2, or P3. However, an explicit statement is not required to support a negative limitation under § 112. See In re Wright, 866 F.2d 422 (Fed. Cir. 1989) (claimed subject matter, including negative limitations, "need not be described in haec verba in the specification for that specification to satisfy the description requirement"); Ex parte Daysh, Appeal No. 2011-010706, p. 4 (BPAI 2012) ("literal support for the claim language is not required" for negative limitation to meet the written description requirement). For purposes of satisfying the written description requirement under § 112(a), a negative limitation is "adequately supported when the specification describes a reason to exclude the relevant limitation," which includes "describing alternative features of the patented invention." Inphi Corp. v. Netlist, Inc., 805 F.3d 1350, 1355-1356 (Fed. Cir. 2015), citing Santuarus, Inc. v. Par Pharm., Inc., 694 F.3d 1344, 1351 (Fed. Cir. 2012). That standard is met with respect to Parent, P2, and P3 in this case.
Examiner's response:
The above argument has been carefully considered and has not been found persuasive.
As set forth above, MPEP 2173.05(i) states: Any negative limitation or exclusionary proviso must have basis in the original disclosure. If alternative elements are positively recited in the specification, they may be explicitly excluded in the claims. See In re Johnson, 558 F.2d 1008, 1019, 194 USPQ 187, 196 (CCPA 1977) ("[the] specification, having described the whole, necessarily described the part remaining."). In the instant case, the prior-filed applications do not appear to disclose the term aprotic solvents generically, thus the prior-filed applications do not provide sufficient support for the limitation “wherein the aqueous topical suspension does not include any aprotic solvents.”
Moreover, MPEP 2173.05(i) states: The mere absence of a positive recitation is not basis for an exclusion. There is no teaching or direction provided in the Parent (‘065), P2 (‘923), and P3 (‘567) that would direct anyone to exclude aprotic solvents. The Parent (‘065), P2 (‘923), and P3 (‘567) disclose solvents generically. The only mention of specific classes of solvents refers to ethylene and/or propylene glycol based solvents, sorbitol based solvents, and non-DMSO solvents. There is no mention of aprotic solvents and while DMSO is an aprotic solvent, a single aprotic solvent is insufficient to provide support for the scope encompassed by aprotic solvents, which includes any solvent lacks acidic hydrogens.
While there is disclosure of excipients that may also function as aprotic solvents, these excipients are disclosed as permeation enhancers, non-active excipients which may aid in or induce penetration of the active benzimidazole agent(s) into the facial skin or ocular tissue and substances that increase the flux of certain active agents through the skin or mucous membranes. While there is also disclosure of certain surfactants that may also increase penetration of active ingredients through solubilization, reduction in interfacial surface tension, or encapsulation of the active ingredient, none of the above listed excipients are listed as such. Thus, the fact that these agents may also function as aprotic solvents is not sufficient to provide written description support for aprotic solvents as these agents are not disclosed as solvents in the previously filed applications. Any negative limitation or exclusionary proviso must have basis in the original disclosure. In the instant case, there is no basis provided in the previously filed applications.
Applicant argues:
Applicant further notes that the cited prior art reference, Jimenez (WO2023249992) is the publication of the PCT application corresponding to Parent and claiming priority to P1. The disclosure in Jimenez, including its Table 9 relied upon in the Office Action, is identical to the disclosure in Parent and is included in the disclosures of P2 and P3. The Office has already found that the 100% formulation in Jimenez's Table 9 communicates to a POSITA that the composition does not include any aprotic solvent. However, the Office has not explained why the Jiminez disclosure in Table 9 is sufficient to teach the claimed limitation for anticipation but the identical disclosure of Table 9 (and similar disclosures in Tables 2, 4, 8, 10, and 17) in Parent, P2, and P3 would be insufficient to convey possession for §112(a) priority purposes.
Examiner's response:
The above argument has been carefully considered and has not been found persuasive.
As noted in the rejection regarding the limitation, wherein the aqueous topical suspension does not include any aprotic solvents, Jimenez teaches mebendazole gel formulations comprising 0.1 % mebendazole, USP, 40% diethylene glycol monoethyl ether (Transcutol P); 1 % hydroxyethylcellulose (Natrosol® 250HR); 43.9% deionized water, and dimethyl isosorbide ([0084] Table 9). The amounts of the ingredients total 100% and does not include any aprotic solvents. Thus, the composition of Jimenez reads on a composition that does not include any aprotic solvents. MPEP 2173.05(i) states: Any negative limitation or exclusionary proviso must have basis in the original disclosure. The mere absence of a positive recitation is not basis for an exclusion. In the instant case, there is no teaching of aprotic solvents in the Parent (‘065), P2 (‘923), and P3 (‘567). Thus, there is no teaching or direction that would arise from the original disclosures of the previous applications that would direct anyone to exclude aprotic solvents.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on July 15, 2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner, except where marked with a strikethrough.
Maintained Objections and/or Rejections
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 1-3, 5, and 6 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Jimenez et al (WO 2023/249992 A2, cited in a previous Office Action).
Regarding claims 1 and 6, Jimenez teaches a topical composition for treating or preventing an inflammatory or autoimmune disease or condition of human skin comprising 0.25 to 20% of one or more benzimidazole compounds, the percentage by weight of the topical composition (claim 1), wherein the carrier comprises a gel (claim 3), wherein the carrier is aqueous (claim 5), wherein the one or more benzimidazole compounds comprises mebendazole (claims 6, 8 and 9), wherein the composition comprises around 15-25% of a glycol based solvent comprising an ethylene glycol based solvent (claim 9), wherein the ethylene glycol based solvent comprises diethylene glycol monoethyl ether (claim 1), wherein the topical composition comprises around 0.01 to 1% mebendazole by weight of the total composition (claim 11). Moreover, Jimenez teaches mebendazole gel formulations comprising 0.1 % mebendazole, USP, 40% diethylene glycol monoethyl ether (Transcutol P); 1 % hydroxyethylcellulose (Natrosol® 250HR); 43.9% deionized water, and dimethyl isosorbide ([0084] Table 9).
Regarding the claimed amount of benzimidazole compounds and the claimed amount of ethylene glycol based solvent, MPEP 2131.03 states:
"[W]hen, as by a recitation of ranges or otherwise, a claim covers several compositions, the claim is ‘anticipated’ if one of them is in the prior art." Titanium Metals Corp. v. Banner, 778 F.2d 775, 227 USPQ 773 (Fed. Cir. 1985) (citing In re Petering, 301 F.2d 676, 682, 133 USPQ 275, 280 (CCPA 1962)).
In the instant case, an amount of 0.1% mebendazole by weight of the total composition and 40% diethylene glycol monoethyl ether (Transcutol P) falls within the instant claimed ranges of claim 1 and thus anticipates the claimed ranges of claims 1.
Regarding the limitation, wherein the aqueous topical suspension does not include any aprotic solvents, Jimenez teaches mebendazole gel formulations comprising 0.1 % mebendazole, USP, 40% diethylene glycol monoethyl ether (Transcutol P); 1 % hydroxyethylcellulose (Natrosol® 250HR); 43.9% deionized water, and dimethyl isosorbide ([0084] Table 9). The amounts of the ingredients total 100% and does not include any aprotic solvents. Thus, the composition of Jimenez reads on a composition that does not include any aprotic solvents.
Regarding claim 2, the composition taught by Jimenez comprises water and hydroxyethylcellulose, diethylene glycol monoethyl ether, and mebendazole.
Regarding claim 3, the composition taught by Jimenez is an aqueous topical suspension in a gel form.
Regarding claim 5, the composition taught by Jimenez is an aqueous topical suspension comprises 1% hydroxyethylcellulose (Natrosol® 250HR). An amount of 1% hydroxyethylcellulose (Natrosol® 250HR) by weight of the total composition falls within the instant claimed range of claim 5 and thus anticipates the claimed ranges of claim 5.
Modified Objections and/or Rejections
Modifications Necessitated by Claim Amendment
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.
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 7 and 29 are rejected under 35 U.S.C. 103 as being unpatentable over Jimenez et al (WO 2023/249992 A2, cited in a previous Office Action) as applied to claims 1-3, 5, and 6 above.
As set forth above, Jimenez teaches a topical composition for treating or preventing an inflammatory or autoimmune disease or condition of human skin comprising 0.25 to 20% of one or more benzimidazole compounds, the percentage by weight of the topical composition (claim 1), wherein the carrier comprises a gel (claim 3), wherein the carrier is aqueous (claim 5), wherein the one or more benzimidazole compounds comprises mebendazole (claims 6, 8 and 9), wherein the composition comprises around 15-25% of a glycol based solvent comprising an ethylene glycol based solvent (claim 9), wherein the ethylene glycol based solvent comprises diethylene glycol monoethyl ether (claim 1), wherein the topical composition comprises around 0.01 to 1% mebendazole by weight of the total composition (claim 11). Moreover, Jimenez teaches an aqueous mebendazole treatment composition for topically treating or preventing an inflammatory or autoimmune disease or condition of human skin, the treatment composition comprising: around 0.01-1% of one or more benzimidazole compounds; around 5-25% of a sorbitol based solvent; and around 15-50% of a glycol based solvent comprising an ethylene glycol based solvent, or a propylene glycol based solvent, or both; and wherein the percentages are by weight (claim 22), wherein the one or more benzimidazole compounds comprises mebendazole (claim 23) and the ethylene glycol based solvent comprises diethylene glycol monoethyl ether (claim 23); wherein the composition further comprises around 0.5-3% of a viscosity modifying agent (claim 24), wherein the viscosity modifying agent is hydroxyethyl cellulose, wherein the composition is a gel (claim 26).
Regarding the claimed amounts of mebendazole, diethylene glycol monoethyl ether, and hydroxyethylcellulose of instant claims 7 and the amounts of mebendazole, diethylene glycol monoethyl ether of instant claim 29, MPEP 2144.05 states: In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). Even a slight overlap in range establishes a prima facie case of obviousness. In re Peterson, 65 USPQ2d 1379, 1382 (Fed. Cir. 2003).
Regarding the limitation, wherein the aqueous topical suspension does not include any aprotic solvents (instant claim 29) or does not include dimethylsulfoxide, methylsuflonylmethane, pyrrolidones, or dimethylacetimede (instant claim 30), Jimenez teaches mebendazole gel formulations comprising 0.1 % mebendazole, USP, 40% diethylene glycol monoethyl ether (Transcutol P); 1 % hydroxyethylcellulose (Natrosol® 250HR); 43.9% deionized water, and dimethyl isosorbide ([0084] Table 9). The amounts of the ingredients total 100% and does not include any aprotic solvents or dimethylsulfoxide, methylsuflonylmethane, pyrrolidones, or dimethylacetimede. Thus, the composition of Jimenez reads on a composition that does not include any aprotic solvents and a composition that does not include dimethylsulfoxide, methylsuflonylmethane, pyrrolidones, or dimethylacetimede.
Taken together, all this would result in the composition of claims 7 and 29 with a reasonable expectation of success.
Response to Arguments
Applicant argues:
The only prior art cited against CIP is Jiminez, which is the publication of the PCT application related to P1 and Parent. Jimenez has a publication date of December 28, 2023. As this publication date is after the June 20, 2023 filing date of Parent, Jiminez does not constitute prior art under 35 U.S.C. § 102(a)(1). Even if the claims in CIP are only entitled to the filing date of P2 (April 18, 2024) or P3 (May 22, 2024) based on the inclusion of Tables 10 and 17 (for example), then Jiminez is still not considered prior art under the grace period exception in 35 U.S.C. § 102(b)(1). The inventors on Jiminez are the same as on CIP, making it an inventor-originated disclosure. The publication date of December 28, 2023 is not more than 1 year before the filing date of either P2 or P3. Therefore, Jiminez is not considered prior art to CIP.
Examiner's response:
The above argument has been carefully considered and has not been found persuasive.
As set forth above, the effective filing date of the instant claims is April 16, 2025. As set forth above, the disclosure of the prior-filed applications, US Application No. 18/212,065 and US Provisional Applications 63/353,907; 63/635,923; and 63/650,567 fail to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. In a review of US Application No. 18/212,065 and US Provisional Applications 63/353,907; 63/635,923; and 63/650,567, disclosure of aprotic solvents was not identified. MPEP 2173.05(i) states:
Any negative limitation or exclusionary proviso must have basis in the original disclosure. If alternative elements are positively recited in the specification, they may be explicitly excluded in the claims. See In re Johnson, 558 F.2d 1008, 1019, 194 USPQ 187, 196 (CCPA 1977) ("[the] specification, having described the whole, necessarily described the part remaining."). In the instant case, the prior-filed applications do not appear to disclose aprotic solvents, thus the prior-filed applications do not provide sufficient support for the limitation “wherein the aqueous topical suspension does not include any aprotic solvents.”
New Objections and/or Rejections
Necessitated by Claim Amendment
Claim Rejections - 35 USC § 103
Claim 30 is rejected under 35 U.S.C. 103 as being unpatentable over Roechling et al (CA 2059602, cited in the IDS filed July 15, 2026) in view of Chow et al (US 2009/0048322 A1, cited in the IDS filed July 29, 2025), Derrieu et al (FR 2,755,824, cited in the IDS filed July 29, 2025) and Sullivan et al (Food and Chemical Toxicology, 2014; 72:40-50).
Roechling teaches a pour-on formulation for the administration of anthelmintics (Abstract). Roechling teaches a preparation which has anthelmintic activity and contains as an active ingredient at least benzimidazole with anthelmintic activity in fine-particle dispersion in a penetration promoting agent (claim 1); wherein the content of the active ingredient is 1-60% by weight (claim 3) in which are employed a penetration-promoting oil as penetration-promoting agent, together with auxiliaries such as emulsifiers, wetting agents, and/or dispersants (claim 4). Roechling teaches a very important group of agents for controlling endoparasitic helminths are suitably substituted benzimidazole (page 1, lines 26-28); including mebendazole (page 3, lines 1-6). Roechling teaches the fine-particle active ingredients can also be dispersed in water in which penetration-promoting oils are emulsified, in which case the water content of these dispersions can be up to 50% by weight (page 4, lines 26-29). A dispersion reads on a suspension composition. Thus, Roechling teaches an aqueous topical composition suspension comprising mebendazole.
Roechling does not teach the composition comprises the elected diethylene glycol monoethyl ether.
However, Chow teaches a drug delivery system comprising a benzimidazole derivative and oil, a surfactant, and a cosurfactant (claim 1), further comprising water (claim 2) wherein the water is at a weight ratio of about 50% (claim 3), wherein the benzimidazole derivative is 5-benzoyl methyl 5-benzoylbenzimidazole-2-carbamate (claims 4 and 5), wherein the cosurfactant is transcutol (claim 8). Chow teaches 5-benzoyl methyl 5-benzoylbenzimidazole-2-carbamate is mebendazole (MZ) [0022] and Transcutol is diethyl glycol monoethyl ether (Table VIII). Thus, Chow teaches transcutol is a suitable excipient in compositions comprising mebendazole, an oil, and water.
Moreover, Derrieu teaches galenic formulation of benzimidazoles for topical use (title); wherein the formulation is useful for treating parasitosis ([0006] and claim 19); galenic formulation comprising at least a benzimidazole in a medium containing at least a nonaqueous vehicle, a nonaqueous co-solvent, a nonionic surface-active agent and a polymer (claim 1), wherein the benzimidazole is mebendazole (claim 2); wherein the nonaqueous co-solvent is diethylene glycol monoethyl ether (claim 5); wherein the formulation can be administered topically (claims 19 and 20). Moreover, Derrieu teaches 2-octyldodecanol and diethylene glycol monoethyl ether are alternatively useful as non-aqueous co-solvent for compositions comprising mebendazole.
Moreover, Sullivan teaches Transcutol® (diethylene glycol monoethyl ether, DEGEE) is commonly used as a vehicle in the formulation or manufacturing in the formulation or manufacturing process of pharmaceuticals, cosmetics, and food additives (Abstract); DEGEE has a long history of use in pharmaceutical applications worldwide in the United States of America, Asia, and Europe; it is an effective solubilizer and is used in oral, topical, transdermal and injectable human and veterinary pharmaceutical products; in recent years it has been widely used as a solvent for topical products on account of three main properties: firstly, it has been shown to solubilize actives that are insoluble in common solvents such as propylene glycol and ethanol; secondly, it modifies the skin penetration properties of active ingredients allowing different drug delivery outcomes to be obtained including enhanced local absorption, a prolonged release depot effect or systemic absorption for transdermal applications; lastly it provides functionality at concentrations which avoid safety and tolerability issues (page 41, right, last paragraph).
As such, since Roechling and Chow teaches an aqueous topical composition suspension comprising mebendazole and 2-octyldodecanol, wherein the compositions do not include dimethyl sulfoxide, methylsulfonylmethane, pyrrolidones, or dimethylacetimede; since Chow teaches transcutol/diethylene glycol monoethyl ether is a suitable excipient in compositions comprising mebendazole, an oil, and water; since Derrieu teaches that 2-octyldodecanol and diethylene glycol monoethyl ether are alternatively useful as non-aqueous co-solvent for compositions comprising mebendazole, and since Sullivan teaches diethylene glycol monoethyl ether is widely used as a solvent for topical products because it has been shown to solubilize actives that are insoluble in common solvents such as propylene glycol and ethanol; it modifies the skin penetration properties of active ingredients allowing different drug delivery outcomes to be obtained including enhanced local absorption, a prolonged release depot effect or systemic absorption for transdermal applications; and provides functionality at concentrations which avoid safety and tolerability issues, it would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to substitute the 2-octyldodecanol penetration-promoting oil with diethylene glycol monoethyl ether an expectation of success, since the prior art establishes that 2-octyldodecanol and diethylene glycol monoethyl ether are alternatively useful as non-aqueous co-solvent and diethylene glycol monoethyl ether is known to be widely used as a solvent for topical products because it has been shown to solubilize actives that are insoluble in common solvents such as propylene glycol and ethanol; it modifies the skin penetration properties of active ingredients allowing different drug delivery outcomes to be obtained including enhanced local absorption, a prolonged release depot effect or systemic absorption for transdermal applications; and provides functionality at concentrations which avoid safety and tolerability issues.
With regard to the limitation “for treating or preventing an inflammatory or autoimmune disease or condition of human skin,” such a limitation of the instant claims fail to patentably distinguish the instant claims over the cited prior art because such a limitation is an intended use of the composition (i.e. an intent to use the disclosed pharmaceutical combination as treatment for corneal damage), which does not impart any physical or material characteristics to the composition that is not already present in the cited prior art. When reading the preamble in the context of the entire claim, the recitation “for treating or preventing an inflammatory or autoimmune disease or condition of human skin” is not limiting because the body of the claim describes a complete invention and the language recited solely in the preamble does not provide any distinct definition of any of the claimed invention’s limitations. Thus, the preamble of the claim(s) is not considered a limitation and is of no significance to claim construction. See Pitney Bowes, Inc. v. Hewlett-Packard Co., 182 F.3d 1298, 1305, 51 USPQ2d 1161, 1165 (Fed. Cir. 1999). See MPEP § 2111.02.
With regard to the limitation wherein at least some of the one or more benzimidazole compounds remain in undissolved form in the aqueous topical suspension, Roechling teaches a very important group of agents for controlling endoparasitic helminths are suitably substituted benzimidazole (page 1, lines 26-28); including mebendazole (page 3, lines 1-6); these agents are sparingly soluble substances (page 3, lines 8-9); it has been found, surprisingly, that fine-particle dispersions (suspensions) of the said benzimidazoles with anthelmintic activity are able (page 3, lines 22-27). Moreover, Roechling teaches an example in which a benzimidazole compound is formulated in a dispersion comprising water and then added to the emulsifier solution. It would have been prima facie obvious to one of ordinary skill in the art to formulate the composition wherein the benzimidazole composition is dissolved in the oil composition and also in dispersion in water which would result in a composition wherein some of the benzimidazole compound remains undissolved in the aqueous topical suspension.
Regarding the limitation wherein the aqueous topical suspension does not include any dimethyl sulfoxide, methylsulfonylmethane, pyrrolidones, or dimethylacetimede, Roechling is silent with regard to the use of either dimethyl sulfoxide, methylsulfonylmethane, pyrrolidones, or dimethylacetimede, thus it is safe to assume the compositions do not contain dimethyl sulfoxide, methylsulfonylmethane, pyrrolidones, or dimethylacetimede.
Regarding the claimed amount of mebendazole of instant claim 30, Roechling teaches the active ingredient is 1-60% by weight (claim 3).
Roechling does not explicitly teach the claimed amounts of benzimidazole.
However, Chow teaches a drug delivery system comprising a benzimidazole derivative and oil (claim 1), further comprising water (claim 2) wherein the water is at a weight ratio of about 50% (claim 3), wherein the benzimidazole derivative is 5-benzoyl methyl 5-benzoylbenzimidazole-2-carbamate (claims 4 and 5). Chow teaches 5-benzoyl methyl 5-benzoylbenzimidazole-2-carbamate is mebendazole (MZ) [0022]. Moreover, Chow teaches the methyl 5-benzoylbenzimidazole-2-carbamate is at a concentration of about 0.9 mg/ml to about 2 mg/ml (claim 22). An amount of 0.9 mg/ml to about 2 mg/ml is equivalent to an amount of about 0.09%-0.2%.
Regarding the amount diethylene glycol monoethyl ether of instant claims 30, the cited art does not explicitly teach the claimed amounts. However, Derrieu teaches diethylene glycol monoethyl ether is a nonaqueous co-solvent (claim 4); is in the composition in an amount of 0.1 to 30% (claim 9). Furthermore, Chow teaches compositions comprising mebendazole, an oil (Miglyol) (claim 6) and a cosurfactant, transcutol (claim 8), wherein the cosurfactant is in an amount of about 6-48%.
It would have been prima facie obvious to one of ordinary skill in the art to utilize the amount of mebendazole taught by Roechling and Chow and the amounts of diethylene glycol monoethyl ether taught by Derrieu and Chow as a starting point for optimizing the amount of mebendazole, diethylene glycol monoethyl ether, and water for use in formulating an aqueous topical composition comprising mebendazole, diethylene glycol monoethyl ether, an oil and water for treating endoparasitic helminths, since Roechling, Chow and Derrieu teach these amounts for formulating similar compositions comprising similar components and because dosage and concentrations are result-effective variables, i.e. a variable that achieves a recognized result. Therefore, the determination of the optimum or workable dosages would have been well within the practice of routine experimentation by the skilled artisan. Furthermore, absent any evidence demonstrating a patentable difference between the compositions and the criticality of the claimed dosage range, the determination of the optimum or workable dosing regimen given the guidance of the prior art would have been generally prima facie obvious to the skilled artisan. Please see MPEP 2144.05 [R-2](II)(A) and In re Aller, 220 F. 2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). ("[W]here the general conditions of claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.").
Taken together, all this would result in the composition of claim 30 with a reasonable expectation of success.
Maintained Objections and/or Rejections
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.
Claim 1-3 and 5-7 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5, 7-10, 12, 16-25, and 27-50 of copending Application No. 18/212,065 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because:
The instant claims are directed to an aqueous topical suspension for treating or preventing an inflammatory or autoimmune disease or condition of human skin comprising 0.01 to 1% of one or more benzimidazole compounds, wherein at least some of the one or more benzimidazole compounds remain in undissolved form in the aqueous topical suspension; and 15 to 45% of an ethylene glycol based solvent; wherein the percentages are by weight of the aqueous topical suspension; and wherein the aqueous topical suspension does not include any aprotic solvents, wherein the aqueous topical suspension further comprises water and hydroxyethylcellulose, wherein the composition is in a gel form.
The copending claims are directed to an aqueous topical composition suspension for treating or preventing a disease or a condition of human skin comprising: 0.01 to 0.075% of one or more benzimidazole compounds, wherein at least some of the one or more benzimidazole compounds remain in undissolved form in the aqueous topical suspension; wherein there are no active agents in the aqueous topical composition suspension other than the one or more benzimidazole compounds; wherein percentages are by weight of the aqueous topical suspension; and wherein the aqueous topical suspension does not include any dimethyl sulfoxide and does not include any dimethylacetamide; wherein the one or more benzimidazole compounds comprises mebendazole; wherein the composition further comprises an ethylene glycol based solvent comprising diethylene glycol monoethyl ether; wherein the composition comprises around 2.5-15% of the diethylene glycol monoethyl ether; wherein the composition further comprises around 0.5-3% of a viscosity modifying agent, wherein the viscosity modifying agent comprises hydroxyethylcellulose. The amounts of the mebendazole, diethylene glycol, monoethyl ether, and hydroxyethylcellulose overlap the instantly claimed amounts.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to arrive at the instantly claimed composition from the composition of the copending claims with a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
With regard to the double patenting rejection, applicant's request for this rejection to be held in abeyance until all other rejections are overcome has been acknowledged. The double patenting rejection is maintained and held in abeyance.
Conclusion
Claims 1-3, 5-7, 29, and 30 are rejected.
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RAYNA B RODRIGUEZ whose telephone number is (571)272-7088. The examiner can normally be reached 8am-5:00pm, Monday - Thursday.
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, Amy L Clark can be reached at 571-272-1310. 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.
/Rayna Rodriguez/ Primary Examiner, Art Unit 1628
Prosecution Insights