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 . Claims 1-5, 7-10, and 12-23 are pending; claims 1-5, 7-10, and 12-20 are examined, claims 21-23 are withdrawn pursuant to Applicant’s election without traverse on 06 October 2025.
Applicant’s arguments, filed 20 March 2026, have been fully considered. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Nucleotide and/or Amino Acid Sequence Disclosures
Summary of Requirements for Patent Applications Filed On or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter “Legal Framework”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
Specific deficiency - This application fails to comply with the requirements of 37 CFR 1.831-1.834 because the “Sequence Listing XML,” as a separate part of the disclosure, is defective, damaged or unreadable.
Refer to document “Sequence Listing in Computer Readable Format is Defective” dated 20 April 2026.
Required response - Applicant must provide:
• A replacement “Sequence Listing XML” part of the disclosure, as described above submitted in accordance with either item 1. or 2.; together with
o A statement that identifies the location of all additions, deletions or replacements of sequence information relative to the replaced “Sequence Listing XML” as required by 37 CFR 1.835(b)(3);
o A statement that indicates support for the replacement “Sequence Listing XML” in the application, as filed, as required by 37 CFR 1.835(b)(4); and
o A statement that the replacement “Sequence Listing XML” includes no new matter as required by 37 CFR 1.835(b)(5).
AND
• A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125, inserting the required incorporation by reference paragraph as required by 37 CFR 1.835(b)(2), consisting of:
o A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
o A copy of the amended specification without markings (clean version); and
o A statement that the substitute specification contains no new matter.
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 1-5, 7-10, and 12-20 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 1 contains the trademarks/trade names “Span-80”. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe the following generic names: sorbitan oleate or sorbitan monooleate (neither are listed in the instant Specification), and, accordingly, the identification/description is indefinite.
Claims 2-5, 7-10, and 12-20 are rejected as they depend from claim 1.
Claim 1 recites wherein the pharmaceutical composition comprises a concentration of 25, 50, or 100 units of Clostridium botulinum. The claim is indefinite because the scope of the claim is unclear. Lines 1-2 of claim 1 recites wherein the pharmaceutical composition comprises one or more proteins of Clostridium botulinum. Therefore it is unclear whether the concentration refers to the one or more proteins of Clostridium botulinum, or of actual Clostridium botulinum. To obviate this issue, it is suggested for the claim to recite --- a concentration of 25, 50 or 100 units of the one or more proteins ---.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 5 recites the broad recitation “biomolecules”, and the claim also recites “antibodies” which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. To obviate this issue, it is suggested for the claim to remove the broader recitation of “biomolecules”.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 9 recites the broad recitations “oil triglyceride” and “vegetable oil”, respectively, and the claim also recites “sunflower seed oil” and “castor oil”, which are the respective narrower statement of the ranges/limitations. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. To obviate this issue, it is suggested for the claim to remove the broader recitations.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 17 recites the broad recitation “therapeutic agents”, and the claim also recites “epidermal growth factors” which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. To obviate this issue, it is suggested for the claim to remove the broader recitation of “therapeutic agents”.
Response to Arguments
The indefiniteness rejections listed above represent the unaddressed or new rejections from Applicant’s amendments.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1-5, 7-10, and 12-20 are rejected under 35 U.S.C. 103 as being unpatentable over Singh et al. (US 2021/0346292 A1, 11/11/2021) (hereinafter Singh) in view of Baker et al. (US 2012/0064136 A1, 03/15/2012) (hereinafter Baker).
Regarding claims 1, 3, 4, 19 and 20, Singh discloses a method of treatment by topically administering an effective amount of pharmaceutical compositions comprising proteins of botulinum toxins or complex thereof, as an emulsion to treat local and systemic conditions including skin problems. The proteins were emulsified with encapsulated microspheres and nanospheres (nanoparticles) (i.e. nanoemulsion) containing propylene glycol (0.3-6%), phenoxyethanol (0.1-5%), sodium hyaluronate (0.01-1%), caprylic/capric triglyceride (0.5-10%), hydrogenated castor oil (1-15%) and Span®-80 (0.01-6%) in water (claim 9, [0017]).
Singh differs from the instant claim insofar as not explicitly disclosing wherein the composition comprises saponin.
However, Baker discloses topical nanoemulsions ([0029]) comprising active agents including botulinum toxin ([0032]). The nanoemulsion may further comprise at least one surfactant ([0028]), including saponin ([0113]).
Accordingly, it would have been obvious to one of ordinary skill in the art to have included a saponin in the composition of Singh since it is a known and effective surfactant suitable for topical nanoemulsions as taught by Baker. Generally, it is prima facie obvious to select a known material for incorporation into a composition, based on its recognized suitability for its intended use. See MPEP § 2144.07.
Regarding the claimed amounts of saponin, it would have taken no more than the relative skills of the one of ordinary skill in the art to have arrived at the claimed range of saponin (i.e. 1 to 10% w/v) through routine experimentation based on the general guidance on level of emulsification desired. Moreover, in any case, the selection of appropriate w/v percentages would appear to require no more than routine testing on the part of the skilled artisan, and so alternatively it would have been obvious to determine workable ranges to arrive at the claimed amounts in % w/v. "[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." See MPEP § 2144.05(II)(A).
Regarding the claimed concentrations of the one or more proteins of Clostridium botulinum, although Singh does not explicitly disclose an amount, the proteins of botulinum toxin is a result effective variable delivering a desired effect. Therefore, it would have taken no more than the relative skills of the one of ordinary skill in the art to have arrived at the claimed range (i.e. 25, 50, or 100 units) through routine experimentation based on the clinical effects desired. Similarly, in any case, the selection of appropriate units of botulinum toxin would appear to require no more than routine testing on the part of the skilled artisan, and so alternatively it would have been obvious to determine workable ranges to arrive at the claimed amounts in units. "[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." See MPEP § 2144.05(II)(A).
Regarding claims 2 and 5, Singh discloses wherein the composition comprises therapeutic protein including various serotypes of botulinum toxin and protein hormones (claim 4) including botulinum toxin A (title).
Regarding claims 7 and 8, Singh discloses wherein the compositions further comprises bioactive peptides including pentapeptide KTTKS (claim 13).
Regarding claim 9, Singh discloses wherein the composition comprises soy-bean oil (claim 11).
Regarding claim 10, Singh discloses wherein the composition comprises water-soluble co-solvents and surfactants, including Tween® 80 (claim 12).
Regarding claims 12 and 13, Singh discloses wherein the composition further comprises humectants including propylene glycol, and emollients including zinc oxide (claim 14).
Regarding claims 14 and 15, Singh discloses wherein the composition further comprises a stabilizer including human serum albumin (claim 15).
Regarding claim 16, Singh discloses wherein the composition is a gel (claim 16).
Regarding claim 17, Singh discloses wherein the composition is emulsified proteins with retinoids (claim 17).
Regarding claim 18, Singh discloses wherein the composition is stabilized at a pH in between 5.5 and 8.0 (claim 18).
Response to Arguments
Applicant mainly asserts on pp. 4-5 of the Remarks filed 20 March 2026 that claim 1 is a specific formulation that through non-routine experimentation using animal models was determined to penetrate deeply into the skin using only a topical administration at specific concentration. Applicant asserts one of ordinary skill in the art would not be able to produce the formulation instantly claimed based on Singh due to the difficulty in testing animal models demonstrating deep penetration through the skin after topical application such that a therapeutic effect is reliably demonstrated, and that Baker teaches completely different compositions, where saponin is just one in a long laundry list of potential nonionic surfactants. Baker teaches a composition merely comprising botulinum toxin A as one in a laundry list of active ingredients that can be added to nanoemulsions. Baker is focused on stable composition but not one proven to be effective for topically treating conditions using one or more of botulinum toxin serotypes A-G. Therefore there is no motivation or a reasonable expectation of success to select saponin to result in a topical formulation able to effectively penetrate a patient’s skin.
The Examiner does not find Applicant’s assertions to be persuasive. Applicant's allegation about inability to produce the formulation due to difficulty in testing animal models demonstrating deep penetration through the skin to demonstrate therapeutic effect reliably, is merely an opinion with conclusory statements. Conclusory statements, unsupported by objective factual evidence, were not found to be of substantial evidentiary value. See MPEP § 716.01(c). As such, Applicant's assertion is unpersuasive since there is Applicant has not provided showings of factual evidence supporting that the nanoemulsions of Singh are incapable of penetrating the skin.
In response to Applicant's assertion that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., deep penetration into the skin and effectively treating conditions through topical administration) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Moreover, it is noted that the instant claims are directed to a composition. Where the components of the composition are taught by the prior art, as long as the component is present in the composition made obvious, there is a reasonable expectation that the functional recitations regarding such a composition are also met, given that the function of compositions is a product of the compositions’ structure. In other words, the component need not be included for the same purpose as Applicant’s reasoning. Similarly, it is not necessary for the prior art to suggest the combination to achieve the same advantage or result discovered by Applicant. See MPEP 2144(IV). In this case, Singh discloses compositions comprising one or more proteins of Clostridium botulinum, and explicitly discloses surface active agents can be added; Baker discloses known and effective surfactants suitable for topically applied formulations. It is not clear to the Examiner how the addition of saponin provides the unexpected results alleged by the Applicant, as Applicant has not provided any objective showings supporting the unexpectedness of adding saponin. As such, Applicant’s assertions are unpersuasive.
Claim 1-5, 7-10, and 12-17 and 19-20 rejected under 35 U.S.C. 103 as being unpatentable over Edelson et al. (US 2011/0212157 A1, 09/01/2011) (hereinafter Edelson) in view of Delgado-González et al. (US 2015/0079137 A1, 03/19/2015) (hereinafter Delgado), further in view of Baker et al. (US 2012/0064136 A1, 03/15/2012) (hereinafter Baker).
Regarding claim 1-5, 7, 9-10, 14-17 and 19, Edelson disclose topically applied ([0033]) nanoemulsions (i.e. nanoparticle composition) comprising at least one therapeutic agent including botulinum toxin (abs) useful in various cosmetic and medical applications ([0008]). The at least one therapeutic agent may be encapsulated by one or more nanoparticles ([0071]). The botulinum toxin refers to any neurotoxin produced by Clostridium botulinum, and includes serotypes A, B, C, D, E, F, G, as isolated or part of a protein complex ([0032]) formulated with a stabilizing agent such as albumin ([0154]) including human serum albumin ([0157]). The at least one therapeutic agent includes a nucleic acid (i.e. instantly claimed biomolecule) (claim 150) or therapeutic antibodies ([0238]). The composition may further comprise surface active agents and/or emulsifiers including polyoxyethylene sorbitan (TWEEN® 60) and sorbitan monooleate (SPAN® 80) ([0283]); antimicrobial preservatives such as phenoxyethanol ([0285]); lubricating agents including hydrogenated vegetable oils ([0287]), for example, castor ([0288]); oils including soybean oil and dimethicone ([0288]) and medium chain triglycerides containing caprylic and capric acids (i.e. caprylic/capric triglyceride) ([0112]-[0114]); water and cosmetically acceptable solvents including propylene glycol in proportions of up to 70% by weight of the total composition ([0318]); and nicotinamide (i.e., vitamin B3 or niacinamide), which is thought to have anti-inflammatory activity and/or to result in increased synthesis of collagen ([0186]). The formulation may be a lotion ([0012]). Between 1 U and about 100 U, or about 50 U of botulinum toxin may be administered to a treatment area ([0264]).
Edelson differs from the instant claim insofar as not explicitly disclosing wherein the composition comprises sodium hyaluronate or saponin.
However, Delgado discloses cosmetic and/or dermopharmaceutical compositions for the treatment and/or prevention of wrinkles (abs) as nanoemulsions ([0052]). The compositions comprise anti-wrinkle and/or antiaging agent including sodium hyaluronate ([0064]).
Baker discloses topical nanoemulsions ([0029]) comprising active agents including botulinum toxin ([0032]). The nanoemulsion may further comprise at least one surfactant ([0028]), including saponin ([0113]).
Edelson discloses wherein the composition may comprise at least one therapeutic agent. Accordingly, it would have been obvious to one of ordinary skill in the art to have included sodium hyaluronate in the composition of Edelson since it is a known and effective anti-wrinkle and/or antiaging agent suitable for topical nanoemulsions as taught by Delgado.
It would have been obvious to one of ordinary skill in the art to have included saponin in the composition of Edelson since it is a known and effective surfactant suitable for topical nanoemulsions as taught by Baker.
Regarding the claimed amounts of propylene glycol, the claimed amounts (i.e. 0.5 to 5% w/v) would have been obvious to one of ordinary skill in the art since they overlap with the ranges of the prior art (i.e. up to 70% by wt.). In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP § 2144.05(I).
Regarding the claimed amounts of phenoxyethanol, sodium hyaluronate, caprylic/capric triglyceride, Span® 80, and saponin, although the prior art does not explicitly disclose amounts of each component, these are result effective variables because they are preservatives, anti-wrinkle agent, oils, emulsifying agents and surfactants, respectively. Therefore it would have taken no more than the relative skills of the one of ordinary skill in the art to have arrived at the claimed ranges of phenoxyethanol, sodium hyaluronate, caprylic/capric triglyceride, Span® 80, and saponin (i.e. 0.1 to 1% w/v; 0.1 to 1% w/v ; 0.5 to 5% w/v; 0.1 to 1% w/v; and 1 to 10% w/v, respectively) through routine experimentation based on the general guidance on desired preservative, anti-wrinkle, oily phase, and emulsification desired. Moreover, in any case, the selection of appropriate w/v percentages would appear to require no more than routine testing on the part of the skilled artisan, and so alternatively it would have been obvious to determine workable ranges to arrive at the claimed amounts in % w/v. "[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." See MPEP § 2144.05(II)(A).
Regarding claim 8, Edelson differs from the instant claim insofar as not explicitly disclosing a claimed peptide.
However, Delgado discloses cosmetic and/or dermopharmaceutical compositions for the treatment and/or prevention of wrinkles (abs) as nanoemulsions ([0052]). The compositions comprise anti-wrinkle and/or antiaging agent including sodium hyaluronate and Argireline® (INCI: acetyl hexapeptide-8) ([0064]).
Edelson discloses wherein the composition may comprise at least one therapeutic agent. Accordingly, it would have been obvious to one of ordinary skill in the art to have included Argireline® in the composition of Edelson since it is a known and effective anti-wrinkle and/or antiaging agent suitable for topical nanoemulsions as taught by Delgado.
Regarding claims 12 and 13, as noted by para. [0030] of the instant Specification, propylene glycol is a humectant and dimethicone is an emollient.
Regarding claim 20, Edelson further discloses wherein the nanoemulsions may be applied topically to a person in need thereof to treat wrinkles (i.e. skin problems) (Example 3).
Response to Arguments
Applicant mainly asserts neither Edelson or Delgado discloses instant claim 1 as amended, and there would not be motivated to produce the specific composition with reasonable expectation of success of being stable and therapeutically effective.
The Examiner does not find the Applicant’s assertion to be persuasive. As this is a 103 obviousness rejection, no one piece of prior art is required to teach each and every claim limitation. As discussed in the rejection, Delgado provides the motivation to incorporate sodium hyaluronate into the composition of Edelson, and Baker provides the motivation to incorporate saponin into the composition of Edelson. See MPEP 2141(III).
Claim 18 is rejected under 35 U.S.C. 103 as being unpatentable over Edelson et al. (US 2011/0212157 A1, 09/01/2011) (hereinafter Edelson) in view of Delgado-González et al. (US 2015/0079137 A1, 03/19/2015) (hereinafter Delgado) and Baker et al. (US 2012/0064136 A1, 03/15/2012) (hereinafter Baker), further in view of Taylor (US 2006/0018931 A1, 01/26/2006).
The disclosure of Edelson as modified has been discussed in detail above, and differs from the instant claim insofar as not explicitly disclosing a pH range.
However, Taylor discloses wherein the stability of botulinum toxin compositions may be enhanced by incorporating a pH buffer ([0077]) to a pH range of approximately 4 to about 7.5 ([0078]).
Accordingly, it would have been obvious to one of ordinary skill in the art to have stabilized the composition of Edelson such that the pH is within the range of about 4 to about 7.5 since it is a known and effective range suitable for botulinum containing compositions as taught by Taylor. The claimed range (i.e. between 5.5 and 8.0) would have been obvious from selecting from this range.
Response to Arguments
Applicant’s arguments have been considered but are moot because new rejections necessitated by Applicant’s amendment have been made.
Conclusion
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 LUCY TIEN whose telephone number is (571)272-8267. The examiner can normally be reached Monday - Thursday 8:30 AM - 6:30 PM EST.
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, SAHANA KAUP can be reached at (571) 272-6897. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/LUCY M TIEN/Examiner, Art Unit 1612
/SAHANA S KAUP/Supervisory Primary Examiner, Art Unit 1612
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