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 .
Current Status
This action is responsive to the amended claims of 11/01/2024. Claims 1-11 are pending and have been examined on the merits.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
The effective filing date is 05/01/2023.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 11/22/2024, 06/30/2025, and 08/07/2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Claim Objections
Claims 2-11 are objected to because of the following informalities. Appropriate correction is required.
In claim 2, please add a comma following “
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”. This will appropriately separate the 3 options of the group from which the compound is selected; i.e., “(I-a), a pharmacologically acceptable salt thereof, and a hydrate of the same”. Dependent claims 3-11 are similarly objected to since they do not rectify the issue.
In claim 11, please add the word “and” before the final option from which the viral disease is chosen; i.e., “; and bovine papillomatosis caused by bovine papillomavirus (BPV).”
Claim Rejections - 35 USC § 112
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 8-9 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.
Claim 8 recites “the dosage form”. This limitation lacks antecedent basis in the claim. Parent claims 2 and 1 do not recite “a dosage form,” but only an “external preparation for skin.” Thus, it is unclear what “dosage form” of the parent claim(s) claim 8 is attempting to further limit. Therefore, the metes and bounds of the claim are undefined rendering the claim indefinite. Dependent claim 9 is similarly rejected since it does not rectify the underlying issue.
To overcome: Applicant could amend claim 8 to “wherein a dosage form of the external preparation is an oleaginous ointment”.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 8-9 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claims 8-9 recite “the dosage form” which is not found in the parent claims 2 or 1. Thus, the claims 8-9 recite a limitation outside of the scope of the parent claims and do not properly further limit the claim from which they depend. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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 1-11 are rejected under 35 U.S.C. 103 as being unpatentable over:
YAMAMOTO (Yamamoto, M. et al., Journal of Clinical Investigation, 2014, 124(8), 3479-3488; provided IDS of 11/22/2024), in view of
ONOGI (WO2009020198; machine translation attached), in view of
WATANABE (JPH09316001, pub.1997; machine translation attached), in view of
HORI (JP2006022057; machine translation attached), and in view of
MASUDA (Masuda, T. et al., International Journal of Pharmaceutics, 2011, 422, 160-169).
The claims are drawn to a composition for skin comprising a compound of Formula (I) and a monohydric higher alcohol of 16-20 carbon atoms or squalane (claim 1); wherein the compound is Formula (I-a) (claim 2). The alcohol is branched (claim 3) and is chosen from 2-octyldodecanol, hexyldecanol, or isostearyl alcohol (claim 4). The compound of Formula (I-a) is present at ~0.5-20% by weight (claim 5), the alcohol/squalane is present at ~1-40% by weight (claim 6), and the ratio of the two components is 1:80 to 20:1 (claim 7). The composition is an oleaginous ointment (claim 8) comprising dispersed crystals of Formula (I-a) (claim 9). The composition is intended for DNA viral diseases (claims 10-11).
Determining the Scope and Contents of the Prior Art:
YAMAMOTO teaches FIT-039
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(Pg. 3481 Fig. 1A) and FIA-348 (Pg. 3481 Fig. 1H) – compounds of Formula (I) wherein W is S and O, respectively. Both compounds have inhibitory activity against HSV-1 replication (Pg. 3481 Fig. 1H). An ointment comprising FIT-039 is applied to skin to treat lesions caused by HSV-1 (Pg. 3483 Fig. 3). A topical dosage form has advantages of delivery to the infection site and reduced risk of adverse effects (Pg. 3485 Right col. ¶3).
ONOGI teaches the compounds KP 1009 and KP 1115 and pharmaceutical salts thereof (Pg. 8 claim 5) – compounds of instant Formula (I) wherein W is O and S, respectively. The compounds are useful for treating HSV-1, HSV-2, HPV, varicella-zoster virus, and herpesviruses such as HHV-8 (Pg. 9 claim 8, Pg. 125-126 ¶234-235, Pg. 16 ¶10). The compounds are formulated in ointments (Pg. 119 ¶222) for transdermal administration (Pg. 129-130 ¶242).
WATANABE teaches a topical preparation for viral skin diseases containing an antiviral at 0.1-10% by weight and squalane at 0.5-80% by weight (Pg. 2-3 claims 1-3). Addition of squalane to a topical antiviral increases clinical efficacy by suppressing inflammation (Pg. 7-8 ¶3-4). The squalane is made by reducing squalene (Pg. 12 ¶12); i.e., the squalane is synthetic. The antiviral and squalane are dispersed in an ointment base with a transdermal absorption enhancer (Pg. 21-22 ¶29), the base includes oils, paraffins, waxes, and higher alcohols such as octyldodecanol (Pg. 22-23 ¶30); i.e., oleaginous.
HORI teaches a transdermal absorption base comprising a branched chain alcohol having 10-30 carbons selected from isostearyl alcohol, hexyldecanol, and octyldodecanol present at 15-50% by weight (Pg. 2 claims 1-3), preferably 30-50% (Pg. 15 ¶15). Transdermal absorption enhancers improve transdermal absorption of drugs by altering skin’s barrier function (Pg. 7-8 ¶5) – classic enhancers like fatty acids experience disadvantageous blooming during storage (Pg. 8 ¶6). The alcohols claimed do not bloom and have excellent transdermal absorption (Pg. 10 ¶8). The base comprises oil, paraffin, or wax (Pg. 12 ¶12). The preparation does not volatilize (Pg. 14 ¶14). The drug contained is absorbed through the skin and exhibits local effects (Pg. 16 ¶17) – the drug is present at 1-60% by weight (Pg. 17 ¶17).
MASUDA teaches for topical administration, amorphous crystal forms have advantages such as enhanced skin permeability; cocrystals of drugs and excipients have great potential for high solubility, high stability, and improved safety (Pg. 160 Right col. ¶1-2). Use of an amorphous cocrystal of antiviral acyclovir in an ointment base resulted in higher skin permeation compared to lone acyclovir – cocrystallization and amorphization improved the physical properties of the drug (Pg. 160 Abstract). MASUDA provides methods for screening cocrystals and amorphization (Pg. 161-162 sect. 2.3-2.5).
Ascertaining the Differences Between the Prior Art and the Claims at Issue:
YAMAMOTO and ONOGI, each, do not teach the instant compound formulated in an ointment with a 16-20 carbon alcohol/squalane.
WATANABE does not teach the instant compound, all of the species of alcohol, nor the exact weight percentages of each component of the preparation.
HORI does not teach the instant compound, squalane, nor the exact weight percentages of each component of the preparation.
MASUDA does not teach the instant compound or a composition thereof.
Resolving the Level of Ordinary Skill in the Pertinent Art:
The level of ordinary skill in the art is represented by an artisan who has sufficient background in the development of an external preparation useful for transdermal absorption of antivirals and possesses the technical knowledge necessary to make adjustments to the excipients to optimize/enhance skin absorption and anti-inflammatory properties. Said artisan has also reviewed the problems in the art regarding transdermal anti-viral compositions and understands the solutions that are widely-known in the art.
Considering Objective Evidence Present in the Application Indicating Obviousness or Nonobviousness:
The instant claims are prima facie obvious in light of the combination of references YAMAMOTO, in view of ONOGI, in view of WATANABE, in view of HORI, and in view of MASUDA.
Regarding claims 1-4, the artisan would be motivated to formulate the compound of Formula (I) (W=S or O) in an external preparation for skin to create an ointment useful for treating viral skin disease since YAMAMOTO and ONOGI each teach the compounds’ utility as such (see all teachings above). To increase clinical efficacy by suppressing inflammation, the artisan would be motivated to add squalane to the preparation, as recognized by WATANABE (Pg. 7-8 ¶3-4). To optimize transdermal absorption by altering the skin barrier and reduce risk of blooming/volatilization, the artisan would be motivated to add isostearyl alcohol, hexyldecanol, and/or octyldodecanol to the preparation, as recognized by HORI (Pg. 7-14 ¶5-6, 8, &14; Pg. 2 claims 1-3). The artisan would have an expectation of success in mixing a preparation comprising squalane and any of the recited alcohols since WATANABE states the preparation may also comprise higher alcohols such as octyldodecanol (Pg. 22-23 ¶30).
Regarding claims 5-7, the artisan would have been motivated to optimize the % weights and corresponding ratios of the ingredients in the external preparation.
MPEP 2144.05(II)(A) provides guidance about the routine optimization of prior art conditions: "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). "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.").”
Furthermore, MPEP 2144.05(I) provides guidance about 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…Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close.”
In the instant case, WATANABE teaches 0.1-10 weight% of the antiviral and 0.5-80 weight% squalane (Pg. 2-3 claims 1-3) – inclusive of 1:80 and 20:1 ratio of antiviral to squalane. HORI teaches 30-50 weight% higher alcohol (Pg. 15 ¶15) and 1-60 weight% drug (Pg. 17 ¶17). These teachings are considered to overlap with/approach the instantly claimed weight %s and ratios. The weight %s (and ratios thereof) of the ingredients are the concentrations of said ingredients in the preparation. Thus, the artisan would recognize the weight % and ratios as result-effective variables, i.e., a variable that achieves a recognized result. Thus, the “concentration,” as recited in the MPEP, may be optimized by routine experimentation. Absent any evidence demonstrating the contrary, the determination of the optimum or workable concentrations of each ingredient (Formula (I) & (I-a) and alcohol/squalane) would have been well within the practice of the artisan given the guidance of the prior art.
Regarding claim 8, the artisan would recognize the preparation of WATANABE and HORI as an oleaginous ointment since both comprise higher alcohols, such as octyldodecanol, which are fatty/oily by virtue of the long chain/many carbons. Further, both WATANABE (Pg. 22-23 ¶30) and HORI (Pg. 12 ¶12) teach a base further comprising oils, waxes, or paraffins – i.e., oleaginous. The artisan would have an expectation of success formulating such ointment since ONOGI teaches the instant compounds formulated in transdermal ointments (Pg. 119 ¶222; Pg. 129-130 ¶242).
Regarding claim 9, the composition of claim 8, as taught by WATANABE (Pg. 21-22 ¶29), has the antiviral dispersed in the oleaginous base. The artisan would be motivated to disperse an amorphous cocrystal of the compound of Formula (I) in the base to enhance skin permeability, stability, and safety of the formulation, as recognized by MATSUDA (Pg. 160 Right col. ¶1-2). The artisan would have an expectation of success since MATSUDA shows amorphous cocrystals in a transdermal composition have such properties compared to a control (Pg. 160 Abstract) and provides methods for screening of cocrystals and amorphization (Pg. 161-162 sect. 2.3-2.5). Such composition would be well within the practice of the artisan.
Regarding claims 10-11, the instant claims are drawn to the composition of claim 1 and recite intended uses thereof. The preparation is expected to be useful for treatment of DNA viral diseases. ONOGI (Pg. 9 claim 8, Pg. 125-126 ¶234-235, Pg. 16 ¶10) and YAMAMOTO (Fig. 1H & Fig. 3), teach the instant compounds and ointments thereof can treat the instantly recited DNA viral diseases. Thus, the transdermal composition comprising such compound(s), made obvious above, would be expected to be suitable for treatment of such diseases. Nothing precludes the use of the composition from such application.
Conclusion
Claims 1-11 are rejected.
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/S.E.B./Examiner, Art Unit 1625
/JOHN S KENYON/Primary Patent Examiner, Art Unit 1625
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