DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Status of the Claims
Pursuant to the amendment dated 09/02/2025, claim 33 has been cancelled. Claims 1-21, 28, 30, 37, and 39 were cancelled in a previous communication. Claims 22-27, 29, 31, 32, 34-36, 38, and 40-44 are pending. Claims 35 and 36 stand withdrawn without traverse.
Claims 22-27, 29, 31, 32, 34, 38, and 40-44 are under current examination.
A terminal disclaimer is on file for US 9,289,442, US 9,757,397; US 10,265,334; and US 10,500,220.
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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 22-27, 29, 31-34, 38, and 40-44 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 and 11-23 of copending Application No. 17/675,654 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because the copending claims fall within the scope of the instant claims.
Inter alia, the claims of the ‘654 application embrace a method of using a composition falling within the scope of the instant claims. Specifically the composition comprises the viscosity increasing agent, hydroxypropyl cellulose, the solvent, ethanol, the humectant, hexylene glycol, and the water repelling agent, cyclomethicone (para 0036 0075 0077 and 0078 of the 654 specification). The composition comprises a diazeniumdiolated co-condensed silica particle formed from the same substances. The amounts of each ingredient embraced by the ‘654 application overlap with amounts required by the instant claims. See MPEP 2144.05 regarding overlapping ranges: “In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists.” The particle size of the NO releasing particles is less than 10 microns (0096 of the ‘654 specification). The examiner considers the shelf life to be an inherent property of the compositions embraced by the ‘654 application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 22-27, 29, 31-34, 38, and 40-44 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 10258564. Although the claims at issue are not identical, they are not patentably distinct from each other because the issued claims render obvious the instant claims.
Inter alia, the claims of the ‘564 patent embrace a method of using a composition falling within the scope of the instant claims. Specifically the “second composition” comprises a second viscosity increasing agent; at least one organic solvent; at least one humectant; at least one water repellent; and a nitric oxide-releasing compound having a diazeniumdiolate functional group, wherein the nitric oxide-releasing compound comprises a NO-releasing co-condensed silica particle formed from the materials as the instant co-condensed silica particle. Turning to the specification of the ‘564 patent to determine the scope of these terms, table 1, col 20 indicates that the second viscosity increasing agent embraces hydroxypropyl cellulose, the solvent embraces isopropyl alcohol, the humectant embraces hexylene glycol, and the water repelling agent, cyclomethicone. The composition comprises a diazeniumdiolated co-condensed silica particle formed from the same substances. The amounts of each ingredient embraced by the ‘564 patent overlap with amounts required by the instant claims. See MPEP 2144.05 regarding overlapping ranges: “In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists.” The particle size of the NO releasing particles is less than 10 microns (see ‘564 patent). The examiner considers the shelf life to be an inherent property of the compositions embraced by the ‘564 patent.
Claims 22-27, 29, 31, 33-34, 38, and 40-44 rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-24 of U.S. Patent No. 11285171.
Although the claims at issue are not identical, they are not patentably distinct from each other because the copending claims render obvious the instant claims.
Inter alia, the claims of the ‘171 patent embrace a composition containing a diazeniumdiolated co-condensed silica particle formed from the same substances as those of the instant claims. The composition comprises an alcohol, which may be ethanol or isopropanol and a mineral oil (i.e. a water repellant) in amounts overlapping with the amounts required by the instant claims. The composition may also contain substances that have humectant properties, such as glycerin, and substances that increase viscosity such as polyethylene glycol. The examiner does not consider the amounts of each component recited in the instant claims to patentably define over the cited patent absent evidence that the claimed range is critical because the ‘171 patent is interpreted to read on any amount of the substances recited in the ‘171 claims. The particle size of the NO releasing particles is considered optimizable. The examiner considers the shelf life to be an inherent property of the anhydrous embodiments embraced by the ‘171 patent.
Response to Arguments
Applicant's arguments filed 09/02/2025 have been fully considered but they are not persuasive. On pages 6-7, Applicant asserts that the ‘654, ‘564, and the ‘171 claims are patentably distinct from the instant claims. This argument is not persuasive because it does not address the specific limitations the examiner pointed out in the rejection. Applicant's arguments fail to comply with 37 CFR 1.111(b) because they amount to a general allegation that the claims define a patentable invention without specifically pointing out how the language of the claims patentably distinguishes them from the references.
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 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 pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) 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 under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claims 22-27, 29, 31, 34, 38, and 40-44 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Peyrot et al. (WO 2000/02953; publication date: 01/20/2000; cited in the IDS filed 11/04/2019; citing the English Human Translation) as evidenced by Labrie (US 6,465,445; issue date: 10/15/2002; cited in the IDS filed 11/04/2019) and as evidenced by Steele et al. (US 2009/0170989; publication date: 07/02/2009) and Schoenfisch et al. (US 2009/0214618; publication date: 08/27/2009; cited in the IDS filed 11/04/2019), in view of Peters EP 1704876; publication date: 09/27/2006), and Davies et al. (US 2004/0067595; publication date: 04/08/2004).
Peyrot discloses a pharmaceutical composition containing no water (anhydrous) comprising (in percent by weight) 2% of anti-acne agent, salicylic acid, 1 % of the viscosity increasing agent, hydroxypropyl cellulose, 4% of the humectant, transcutol (i.e. diethyleneglycol monomethyl ether, see Labrie, col 35, lines 25-27, and see Steele 0035, which discloses that diethyleneglycol monomethyl ether has humectant properties), 50% of the solvent, ethanol, and 20 % of the water repellent, cyclomethicone (example 1, page 6).
The composition disclosed by Peyrot differs from the composition instantly claimed in that the composition does not comprise diazeniumdiolated co-condensed silica particles.
Schoenfisch discloses NO-releasing particles intended to act as an active pharmaceutical agent (abstract) made from co-condensed silica (para 0068, lines 1-2), comprising diazeniumdiolate as the NO donor (para 0064, lines 1-2 and examples 8/9, page 21). The NO-releasing particles have particle size ranging from 200-300 nm (para 0361; limitation of instant claim 11) and release nitric oxide upon contact with water (i.e. they are a water reactive API; para 0333, lines 3-4).
Peters discloses that NO-releasing devices (i.e. a source of nitric oxide) can be used to treat acne (abstract).
It would have been prima facie obvious to use the NO-releasing particles made from co-condensed silica comprising diazeniumdiolate as the NO donor in Peyrot’s invention. One having ordinary skill in the art would have recognized that the NO released from the particles would function as an anti-acne agent in view of Peters. Accordingly, it would be obvious to combine the NO releasing particles of Schoenfisch with Peyrot’s composition containing anti-acne agents because these agents were known to serve the same purpose. See MPEP 2144.06. One would have had additional reasonable expectation of success because Schoenfisch discloses that the particles can be formulated in a topical composition (Schoenfisch: claim 63) and can be formulated as a suspension in an anhydrous composition comprising a thickening agent (0314). The examiner notes that the formulation of Peyrot/Schoenfisch would be a suspension as the particles are silica and would not dissolve in an ethanolic composition.
With regard to the shelf life of the NO source required by instant claim 22, the relevant disclosures of Peyrot, Peters, and Schoenfisch are set forth above. As noted above, Schoenfisch discloses that NO is released from the particles as soon as they are exposed to an aqueous environment. As noted above, Schoenfisch also discloses that formulations containing the particles may also contain excipients such as suspending, thickening, stabilizing, dispersing agents in aqueous or non-aqueous carriers (0314 and 0316).
Davies also discloses that nitric oxide is highly labile in aqueous composition with a half-life of 10 to 30 seconds in aqueous solution (0003).
One having ordinary skill in the art would be motivated to optimize the shelf life of any pharmaceutical in order for the product to be useful to the patient for the maximum amount of time (e.g. at least 80% of the initial amount after 12 weeks). One would do so by selecting ingredients known to be chemically compatible with each other and the active agent. One would be motivated to choose, for example a non-aqueous composition because nitric oxide is highly labile in aqueous composition with a half-life of 10 to 30 seconds in aqueous solution. One would have been particularly motivated to store any product containing Schoenfisch’s particles, which rapidly release their NO (i.e. lose their therapeutic effect) upon exposure to water, in a vehicle that does not contain any water in order to provide a reasonable shelf life for the active agent within the product. One would have reasonable expectation of success optimizing the composition for storage because anhydrous topical vehicles were well known in the art at the time of the instant invention and because removing water from the vehicle would improve the stability of NO. For this reason, the examiner does not consider the limitations of instant claims 26, 27, 29 and 37-39 to patentably define over the prior art. With regard to claim 26, it is obvious to store any pharmaceutical composition in a package for ease of storage and handling.
With regard to claim 23, as noted above, Schoenfisch discloses particle size of 200-300 nm.
With regard to claim 24, the amount of ethanol in Peyrot’s example composition is 50%; however, the proportion of ethanol relative to hydroxypropylcellulose would affect the viscosity of the composition. As there may be different esthetic preferences for viscosity, the examiner does not consider the limitation on amount of alcohol to patentably define over the prior art. Please refer to MPEP 2144.05(II)(A): Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See also Peterson, 315 F.3d at 1330, and 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages”.)
With regard to claim 25, as noted above, the solvent is ethanol.
With regard to claims 31 and 34, as noted above, the composition disclosed by Peyrot contains 1 percent of the viscosity increasing agent hydroxypropylcellulose, 50% ethanol, 4% of the humectant diethyleneglycol monomethyl ether. The composition disclosed by Peyrot differs from the composition instantly claimed in that the amount of cyclomethicone falls just outside the range allowed by claim 34; however Peyrot discloses a preferred range for cyclomethicone in the gel formulation of 18-22%. MPEP 2144.05(1) states that prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985).
With regard to claim 33, as noted above, the composition contains both diethyleneglycol monomethyl ether and the water repellant cyclomethicone.
With regard to claim 40, Peyrot discloses a homogenized composition (see pages 18-19, which disclose vigorous stirring, which the examiner considers to embrace homogenization).
With regard to claims 22 and 41-44, Schoenfisch discloses diazeniumdiolated co-condensed silica particles comprising either AEAP3 or MAP3 and TMOS or TEOS (0158, 0370, and 0253) i.e. the diazeniumdiolated co-condensed silica particles are diazeniumdiolate-functionalized polysiloxane macromolecules.
Claim 32 is rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Peyrot et al. (WO 2000/02953; publication date: 01/20/2000; cited in the IDS filed 11/04/2019; citing the English Human Translation) as evidenced by Labrie (US 6,465,445; issue date: 10/15/2002; cited in the IDS filed 11/04/2019) and as evidenced by Steele et al. (US 2009/0170989; publication date: 07/02/2009); in view of Peters EP 1704876; publication date: 09/27/2006) and Schoenfisch et al. (US 2009/0214618; publication date: 08/27/2009; cited in the IDS filed 11/04/2019) as applied to claims 22-27, 29, 31, 34, 38, and 40-44 above, and further in view of Horstmann et al. (US 5,912,008; issue date: 06/15/1999; cited in the IDS filed 11/04/2019).
The relevant disclosures of Peyrot, Peters, and Schoenfisch are set forth above. Peyrot discloses that the diethylene glycol monomethyl ether (i.e. transcutol) serves as a permeation enhancer in their composition (English machine translation: page 7, lines 12-13). Neither of these references discloses including hexylene glycol in the composition.
Horstmann discloses that both diethylene glycol monomethyl ether and hexylene glycol were known to serve as permeation enhancers for topical drug delivery formulations. Therefore, it would have been prima facie obvious to substitute the diethylene glycol monomethyl ether disclosed by Peyrot with hexylene glycol at the time of the instant invention because both agents were known at the time of the instant invention to serve the purpose of enhancing active agent permeation into the skin. Please see MPEP 2144.06 regarding art-recognized equivalents and MPEP 2144.07 regarding art-recognized suitability.
Response to Arguments
Applicant's arguments filed 09/02/2025 have been fully considered but they are not persuasive.
On pages 8-9 in several locations, Applicant argues that there is not teaching, suggestion or direction in the combination of cited references to the particular claimed composition.
The examiner respectfully disagrees. As noted above, Schoenfisch discloses that the particles release nitric oxide upon contact with water (i.e. they are a water reactive API; para 0333, lines 3-4). Moreover, as noted in the rejection supra, it was known at the time of the instant invention that NO is labile in aqueous solutions. One having ordinary skill would therefore immediately have recognized the benefit of formulating the NO-releasing particles in any anhydrous composition in terms of stability of the active ingredient. As such, there was motivation in the cited prior art to arrive at the claimed invention. Regarding Applicant’s arguments that the combination of cited references do not direct one to the “particular claimed composition”, the examiner points out that the composition is claimed quite generally by only routinely used categories of ingredient, see claim 22.
On page 8, Applicant argues “where what was ‘obvious to try’ was to explore a new technology or general approach that seemed to be a promising field of experimentation, where the prior art gave only general guidance as to the particular form of the claimed invention or how to achieve it”, citing In re Kubin.
This argument does not apply because the fact pattern in In re Kubin does not match the fact pattern of the instant case. In the instant case, Applicant claims generic categories of well-known excipients for topical compositions and lacking water with the unsurprising outcome that a water-labile active degrades less in a non-aqueous environment; one having ordinary skill in the art would have immediately understood that storing a composition that is labile in water in a non-aqueous vehicle would have benefits in terms of reduced degradation of the labile active agent. Thus, the scenario of a “new technology or general approach that seemed to be a promising field of experimentation, where the prior art gave only general guidance as to the particular form of the claimed invention or how to achieve it” is not at all applicable to the instant case. The examiner does not rely on an “obvious to try” rationale and any arguments in traversal of the rejection on these grounds are not persuasive because they do not reflect the reasoning underlying the obviousness conclusion.
On page 8, Applicant argues that Schoenfisch does not describe an anhydrous composition including diazeniumdiolated co-condensed silica particles as claimed and that maintains the ability to release at least 80% of the initial amount of nitric oxide after 12 weeks in an unopened package at a temp of 1-12C. On pages 8-9, Applicant argues that Davies does not provide information regarding stability of diazeniumdiolated co-condensed silica particles in anhydrous compositions. Applicant argues further that there was lack of any reasonable expectation of success of achieving the claimed functional limitation regarding ability to release 80% of the initial amount of nitric oxide after 12 weeks in an unopened package stored between 1-12C.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Also as explained previously, Schoenfisch discloses that the particles release nitric oxide upon contact with water (i.e. they are a water reactive API; para 0333, lines 3-4). The examiner maintains that Davies is relevant to NO stability of any composition containing NO. One having ordinary skill in the art would have recognized that Schoenfisch’s particles would begin to release their NO upon contact with water because Schoenfisch discloses that the particles release nitric oxide upon contact with water (i.e. they are a water reactive API; para 0333, lines 3-4). Moreover, as noted in the rejection supra, it was known at the time of the instant invention that NO is labile in aqueous solutions. One having ordinary skill would therefore immediately recognize the benefit of formulating the NO-releasing particles in any anhydrous composition in terms of stability of the active ingredient. Moreover, one having ordinary skill, i.e. a formulations scientist, would have been motivated to formulate the NO-releasing particles of Schoenfisch in a vehicle in which they would be least likely to degrade because their degradation would lead them to be ineffective for their therapeutic purpose of releasing NO. In view of Schoenfisch, one would have recognized that the particles begin to release NO on contact with an aqueous environment, and would have therefore sought to store them in any non-aqueous environment so that the maximal amount of NO is releasable during application in the presence of water. Any anhydrous medium for storage and subsequent delivery is therefore considered prima facie obvious. The benefits of storage in anhydrous media would have been immediately obvious in view of Schoenfisch’s disclosure that the NO is released upon exposure to water.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KATHERINE PEEBLES whose telephone number is (571)272-6247. The examiner can normally be reached Monday through Friday: 9 am to 3 pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Ali Soroush can be reached at (571)272-9925. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KATHERINE PEEBLES/ Primary Examiner, Art Unit 1617