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 .
Status of claims / Response to Amendment
This office action is in response to an amendment filed on October 27, 2025.
Claims 1-2, 4-22 were previously pending. Applicant amended claims 1-2, 4-7, 9, 11, 13, 15-16, 18-20 and 22; cancelled claims 10, 12, 14 and 17. Claims 23-24 are newly added.
Claims 1-2, 4-9, 11, 13, 15-16 and 18-24 are currently pending and under consideration.
Applicant's claim amendments and arguments overcame the following objection and rejections:
Objection to claim 4;
Rejections (A)-(J) of Claims 1-2 and 4-22 under 35 U.S.C. 112(b);
Rejections of Claim 12, 14 and 17 under 35 U.S.C. 112(d);
The previously set forth 102 and 103 rejections have been withdrawn in view of the recent claim amendment filed on October 27, 2025, which added new limitations to the claims, that were not considered in the previous rejections.
This office action contains new grounds of 102 and 103 rejections necessitated by Applicant's amendments. Although the claims were previously rejected as being unpatentable over the same reference(s), Applicant's amendments have necessitated the inclusion of new grounds of rejections in this Office action.
All other previously presented objection and rejections are maintained for reasons given in the "Response to Arguments" section following each maintained objection/rejection. Applicant' s amendments and arguments have been thoroughly reviewed, but are not persuasive to place the claims in condition for allowance for the reasons that follow.
This office action contains new grounds for rejection necessitated by amendment.
Priority -- Updated
For the instant claims 1-2, 4-9, 11, 13, 15-16 and 18-24 in this U.S. Application, the applicant claims priority of Foreign Application FRANCE 1906830 (certified English translation submitted on 10/27/2025), which has a filling date on 06/24/2019.
Objection to Specification --- New
The disclosure is objected to because of the following informalities:
- Page 9, line 17 in the specification: "early ageing of the sin" should read "early ageing of the skin."
Objection to Specification --- Maintained
The disclosure is objected to because of the following informalities:
- Page 14, line 27 of the specification contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Response to Amendment
Applicant's amendment to the specification (shown below) is acknowledged. However, it is insufficient to overcome the objection because the amended specification still contains the prefix http://. References to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
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Claim Interpretation -- Updated
In evaluating the patentability of the claims presented in this application, claim terms have been given their broadest reasonable interpretation (BRI) consistent with the specification, as understood by one of ordinary skill in the art, as outlined in MPEP§ 2111.
Regarding claim 1, it recites "a method for diagnosis of early ageing of the skin" in the preamble, this claim language is interpreted as descriptive language that does not distinguish the claimed method from prior art methods that disclose all the claimed steps.
MPEP§ 2111.04 states: "Claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed, or by claim language that does not limit a claim to a particular structure."
Here, the claim body does not include any step of diagnosis. In fact, the body only requires determining level of a marker. In other words, the preamble at most states the intended outcome of the claimed method and makes no manipulative difference. Therefore, the claimed method does not distinguish itself from prior art that discloses the determining step.
For the purpose of applying prior art, claim 1 recites "determining in a skin sample of the subject the level of a first marker of fungi comprising a nucleic acid encoding an ITS 1 (« Internal Transcribed Spacer 1 ) region of sequence at least 90 % identical to sequence SEQ ID NO: 1."
Under BRI, this step is interpreted to require determining the level of a marker, of fungi that comprise a nucleic acid sequence at least 90% identical to SEQ ID NO: 1. Thus, this determining step is interpreted to not require detecting the specific sequence itself, only detecting any maker of any fungi meeting this description. This interpretation aligns with the specification, which does not explicitly describe any method step of specifically detecting SEQ ID NO: 1.
Thus, any step in the prior art detecting a marker of fungi comprising a sequence at least 90 % identical to sequence SEQ ID NO: 1 would meet this limitation.
For the purpose of applying prior art, claim 1 recites "an ITS 1(< Internal Transcribed Spacer 1 >) region of sequence at least 90 % identical to sequence SEQ ID NO: 1," it is interpreted that the "sequence at least 90 % identical to sequence SEQ ID NO: 1" is the sequence that comprise the ITS1 region. However, the claim does not specify which portion of the sequence at least 90% identical to SEQ ID NO: 1 encodes the ITS1 region, nor does the specification define any nucleotide positions or provide any criteria for identifying the ITS1 region within the sequence.
This limitation was previously rejected in the Non-Final Office Action (04/29/2025, at page 7) under 35 USC § 112(b) on the basis that, it is unclear whether the entire sequence of SEQ ID NO:1 is considered to encode ITS1, or only a portion, and what constitutes an ITS1 region in this context.
Applicant's remarks filed on October 27, 2025, at page 8 provides the following clarification regarding claim interpretation on the record:
"The expression "an ITS 1 region of sequence at least 90% identical to SEQ ID NO: l" was considered unclear by the Examiner, who questions whether the entire sequence codes for ITS 1 or just a portion of it, and what constitutes ITS 1.
In the context of fungal research, the ITS 1 region is well known to those skilled in the art and is part of routine analysis. As specified on page 4 of the application, SEQ ID NO: 1 is a sequence representative of the ITS1 of fungi of the genus Candida. SEQ ID NO: 1 therefore comprises the entire ITS1 sequence.
Furthermore, a simple sequence alignment would allow those skilled in the art in the absence of undue experimentation upon being made aware of the present disclosure.to determine whether their sequence includes a portion that is at least 90% identical to SEQ ID NO: 1.
Moreover, it is noted that according to the Examiner the ITS 1 fungal marker is used routinely (paragraph bridging pages 15 and 16 of the Office Action)." [emphasis added]
The Applicant's remarks indicate that the entire sequence of SEQ ID NO:1 represents the ITS1 region. As a result, the prior 112(b) rejection has been withdrawn, and the claim interpretation has been updated accordingly.
Claim Rejections - 35 USC § 112(b) -- New Grounds
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.
Claims 23 is rejected under 35 U.S.C. 112(b), 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 23 is indefinite for reciting "treating the skin of the subject diagnosed as showing early ageing of the skin with a cosmetic composition allowing reducing and/or showing early ageing of the skin." A cosmetic composition allowing "reducing and showing early ageing of the skin" appears contradictory. It is unclear how a composition can simultaneously reduce and show signs of early aging.
Claim Rejections - 35 USC § 112(a) -- Maintained with updates
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
Claims 1-2, 4-9, 11, 13, 15-16 and 18-24 are rejected under 35 U.S.C. 112(a) as failing to comply with the written description requirement. The claims contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 1 recites "[a] method for diagnosis of early ageing of the skin in a subject," which lacks written description support.
Accordingly to MPEP 2163 (written description requirement), the specification must clearly demonstrate that the inventor was in possession of the claimed invention at the time of filling.
In this instant case, the specification does not reasonably convey to a skilled artisan that the inventors had possession of the claimed method, as it fails to describe any "method for diagnosis of early ageing of the skin in a subject" with sufficient detail.
The only example in the specification describes:
“the identification of a signature comprising 8 fungi which are significantly modulated in skin samples of individuals exposed to chronic pollution (on the basis of detection of high levels of pollutants in hair samples of the individuals).” (page 12)
The example involves collecting skin samples from subjects residing in two cities in China, one with high levels of pollutant PAHs (polycyclic aromatic hydrocarbons) in the air (Baoding), and the other with lower levels (Dalian).
The specification states that “on clinical level, increased severity was observed for almost all facial signs including wrinkles and pigmentary disorders in individuals living in Baoding” (page 12), indicating that most subjects in Baoding would meet the applicant's own definition of early aging. Fungal composition difference between these predefined groups (normal skin vs. early aging) are then analyzed statistically, using Operational Taxonomic Unit (OTU) to calculate mean differences (pages 14-16).
The application's disclosure fails to support possession of the claimed diagnosis method for the following reasons:
First, the disclosure does not have sufficient written description support for "diagnosing." The definition for diagnosis is "identifying a disease from its signs and symptoms" (merriam-webster.com/dictionary/diagnosis). The application's disclosure does not describe any specific method steps or provide any example, with sufficient detail for identifying early aging in a subject using fungal markers, as described in the claim. Instead, the example compares fungal compositions from subjects already classified as normal skin or early aging based on dermatological evaluation. Diagnosis requires starting with a subject with unknown condition as input and providing a specific diagnosis as output, whereas the example only correlates fungal composition with predefined skin condition categories.
Second, the application does not have written description support for pan-diagnosis of early aging of the skin, irrespective of pollution. The claim broadly defines “early aging of the skin” as having features such as presence of lines and/or wrinkles, large macules, lentigo simplex and/or red patches; encompassing a wide range of skin conditions, regardless of air pollution level. However, the disclosure only describes fungal microbiome variations resulting from pollution, specifically PAHs. This indicates the observed changes in fungal composition result from exposure to pollutant, rather than reflecting a general indicator for early aging of the skin. The disclosure indicates that both the "early aging of the skin" phenotype and the changes in fungal compositions are results of air pollution. However, it fails to consider whether the observed correlation between the "early aging of the skin" phenotype and the changes in fungal composition would still exist in the absence of air pollution.
Third, the application's disclosure does not address whether fungal composition correlates with skin condition, when air pollution is controlled. Both fungal composition and skin condition appear to respond to changes in pollution level in the example, thus changes in fungal composition might not independently indicate early aging. Without controlling for the pollution factor, fungal composition cannot be determined as a reliable marker for early aging. Without resolving this confounding factor, the disclosure fails to demonstrate a dependable relationship between fungal markers and skin condition for diagnostic purposes.
Therefore, the application's disclosure does not meet the written description requirement under 35 U.S.C. 112(a), for there is insufficient disclosure that convey to a person skilled in the art that the inventor was in possession of the claimed "method for diagnosis of early ageing of the skin in a subject" at the time of filling.
Claims 2, 4-9, 11, 13, 15-16 and 18-24 are rejected because they depend from claim 1 and inherit the deficiencies of the base claim.
Repones to Arguments
Applicant's arguments below have been fully considered but are not found persuasive.
"The rejections of claims 1-2 and 4-22 are rejected under 35 U.S.C. § l 12(a) as failing to comply with the written description requirement are not deemed tenable.
According to the Office Action, the reference to a "method for diagnosing signs of
premature aging" would lack written support. Although the application does not provide, in the example section, a diagnostic method, this method is described in the description. Furthermore, the example demonstrates that fungal populations can be used as biomarkers.
According to the Office Action, the application would not provide sufficient support for the general diagnosis of signs of skin aging independently of pollution. According to the Examiner, the application would show a link between exposure to pollution and the composition of the fungal population, rather than with premature skin aging.
However, contrary to this conclusion, statistical tests were actually carried out in relation to skin aging classification, and not pollution. Moreover, a significant proportion of women in the "aged skin" category came from the less polluted area (37 women out of 90).
It was also pointed out in the Office Action, that in the example, skin condition and fungal population appear to be influenced by pollution, and thus a change in fungal population may not indicate aging, because pollution would be a confounding factor.
However, the results of the statistical tests in the application actually focus on the
separation between normal skin and skin showing signs of premature aging (see method 1 ). The fact that these results were obtained by considering populations from two cities with different types of pollution clearly demonstrates the robustness of the identified biomarkers, rather than demonstrating that pollution is a confounding factor.
In particular, Figure 1 ( corresponding to method 2) clearly shows that it is possible, based on OTUs, to differentiate between people exposed to PAHs (included in the ellipse), and those showing signs of premature aging (represented in circles).
Moreover, even if some experimentation were necessary compliance with 35 U.S.C. § 112(b) would not be precluded. Only undue experimentation causes an issue or problem. Please see Hybritech, Inc. v. Monoclonal Antibodies, Inc., 231 U.S.P.Q. 81 (Fed. Cir. 1986). Also, see In re Angstadt, 537 F.2d 498, 504, 190 USPQ 214, 219 (CCPA 1976) and Ex Parte Hicks et al. Appeal 2007-2715 (Board of Patent Appeals and Interferences, November 13, 2007, application 10/200,431) (Informative Opinion)" (Remarks, page 8-9)
Therefore, Applicant appears to argue that there is support in the disclosure for the general diagnosis of signs of skin aging independently of pollution, because "statistical tests were actually carried out in relation to skin aging classification, and not pollution" and "Figure 1 ( corresponding to method 2) clearly shows that it is possible, based on OTUs, to differentiate between people exposed to PAHs (included in the ellipse)."
Applicant's argument is not persuasive, as it mischaracterizes both the general disclosure of the invention and the working examples cited.
First, the present specification expressly describe the invention as a method for finding that "skin samples from individuals presenting with early ageing of the skin and exposed to chronic pollution have significantly different levels of some fungi compared with individuals not showing said early ageing and not exposed to such pollution" :
"There is therefore a major need for methods to diagnose early ageing of the skin that in
particular is pollution-related.
The present invention meets this need.
The present invention results from the unexpected finding by the inventors that skin samples from individuals presenting with early ageing of the skin and exposed to chronic pollution (based on the detection of high levels of pollutants in hair samples thereof) have significantly different levels of some fungi compared with individuals not showing said early ageing and not exposed to such pollution." (Specification, Page 1).
Therefore, according to the express language in the specification, the disclosed invention particularly relates to skin conditions due to pollution exposure.
Second, as described in Method 2 and depicted in Figure 1 (derived from Method 2), shown below for clarity of the record, measured air pollution levels or PAH levels from the subjects (subject's exposure to PAH is measured in hair samples, see page 12, lines 23-25) are required for the analysis. These values are used to generate the clustering shown in Figure 1, which forms the basis of the "diagnosis" described in the disclosure, with pollution level represented on the horizontal axis.
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"Method 2: Comparison of fungal relative abundance profile in relation to historical grouping of subjects versus PAH compounds (Baoding/Dalian database).
With regard to analysis of global correlation with PAH, pre-filtering was performed on OTU relative abundance. OTUs with relative abundance lower than 0.1% among all individuals were removed. Also, CSS standardisation («Cumulative sum scaling u) was applied which corrects biases in the assessment of differential abundance induced by TSS («Total sum scaling») standardisation. Among the OTUs, 69 were selected for the fungi. PAH measurements were log-transformed to follow Gaussian distribution. A total of 202 individuals with OTU and PAH data were included in the analysis. With a view to variable selection, Sparse Canonical Correlation Analysis (sCCA) was performed to select the OTU and PAH descriptors which were active in relationships between blocks. The sparsity parameters of sCCA were selected via permutation procedure using the MutiCCA.permute function of the PMD R package (Witten et al. (2009) Biostatistics 10:515-534; Tenenhaus et al. (2014) Biostatistics 15:569-583). Finally, to obtain common representation of individuals in the 2 blocks, hierarchical multi-block analysis (MAXVAR-A) was performed using the RGCCA R package (Tenenhaus et al. (2017) Psychometrika 82:737-777). Subjects showing signs of early ageing are surrounded by a circle in FIG. 1.
For diagnosis, the new profile must be compared with the grouping. If it is contained within the left-hand ellipse, the subject tests positive and shows early ageing of the skin." (Specification, page 17)[emphasis added]
Accordingly, Applicant's arguments are not persuasive. The rejections are properly maintained and have been updated to reflect the recent claim amendments.
Claim Rejections - 35 USC § 101 -- Maintained with updates
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-2, 4-9, 11, 13, 15-16 and 18-24 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more.
Independent claim 1 is drawn to a method for diagnosis of early ageing of the skin in a subject, comprising a step of determining in a skin sample of the subject the level of a marker of fungi comprising a nucleic acid encoding an ITS 1(< Internal Transcribed Spacer 1 >) region of sequence at least 90 % identical to sequence SEQ ID NO: 1.
Therefore, the claims are directed to the step to determine a level of a fungal marker in a sample, for diagnosis of early skin aging.
Following the analysis below the claims are not patent eligible under 35 U.S.C. 101.
Step 1 - Whether the Claim is to a Statutory Category: YES. The claims are drawn to a method, therefore to one of the of statutory categories.
Step 2A Prong 1 - Whether the Claim Recite an Abstract idea, Law of Nature, or Natural Phenomenon: Yes. The claim recites a judicial exception, namely a law of nature of natural phenomenon. Specifically, the claim recites the natural correlation between fungi (as measured using marker such as ITS1) and skin aging.
As stated in MPEP 2106.04(b)(I), laws of nature and natural phenomena, as identified by the courts, include naturally occurring principles/relations and nature-based products that are naturally occurring or that do not have markedly different characteristics compared to what occurs in nature.
In this instant case, the judicial exception is the natural correlation of fungi (with presence indicated by their marker) and an early aging skin condition.
In conclusion, the claims recite laws of nature and natural phenomena.
Step 2A Prong 2 - Whether the Claim Recite Additional Elements that Integrate the Judicial Exception into a Practical Application: No. The claim as a whole do not integrates the exception into a practical application of that exception.
The additional element in the claim do not transform the claimed natural phenomena to something that are markedly different than their naturally occurring counterparts in their natural state, nor does it integrate the recited judicial exception into a practical application of the exception. The only required step in claim 1 is determining the level of the marker.
While the claim describes additional details about the recited fungi, including the presence of an ITS1 region within a sequence at least 90% identical to SEQ ID NO: 1, this too represents a natural phenomenon. The only additional element is merely detecting a marker, generically encompass any detection method. Although ITS1 is a fungal marker, yet this is a very routine and conventional fungal marker and highly conserved across fungal community. Therefore, the additional element of detecting ITS1 is merely an instruction to generically apply conventional methods of detection fungi.
The claim's preamble recites "a method for diagnosis of early ageing of the skin in a subject," but this does not integrate the judicial exception into a practical application nor render the claim patent-eligible. The courts have repeatedly held that diagnostic claims based on naturally occurring correlations, without additional elements that impose meaningful limits on the judicial exception, are ineligible under 35 U.S.C. 101. See Athena Diagnostics, Inc. v. Mayo Collaborative Servs., LLC, 927 F.3d 1333, 1352 (Fed. Cir. 2019) (en banc) (Moore, J., dissenting) (expressing that the current interpretation of Section 101 eliminated diagnostic testing as patentable subject matter). Diagnostic testing claims fail because the novel step across the claims involves the mental step of reading the results and comparing them to a known relationship, or otherwise observing a natural law. See id. at 1336 (Lourie, J., concurring) (acknowledging that the only consistent interpretation of Supreme Court decisions resolving issues of patentable subject matter requires invalidating patents for diagnostic tests that merely observe natural laws); Roche Molecular Sys., Inc. v. CEPHEID, 905 F.3d 1363, 1372 (Fed. Cir. 2018) (explaining that observation of the relationship between the sample and known phenomena does not involve an inventive concept).
Step 2B- Whether a Claim Amounts to Significantly More: No. In this instant case, the claims, when considered as a whole, do not recite any inventive concept with additional elements that amount to significantly more than the judicial exception.
The claims do not appear to add markedly different characteristics that significantly modify or use the naturally occurring correlation in a manner that is not naturally occurring.
Claim 1 requires only the step of determining the marker level of fungi in a sample.
Dependent claims 4 and 11 add comparing and determining steps, which merely observe natural laws and constitute abstract ideas. Claim 6 recites, at a high level of generality, determining the marker level through PCR amplification and sequencing; but this merely represents well-understood, routine, conventional activity in the life science arts, as recognized by the courts. See University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 764, 113 USPQ2d 1241, 1247 (Fed. Cir. 2014).
Dependent claim 23 recites "treating the skin of the subject diagnosed as showing early ageing of the skin with a cosmetic composition allowing reducing and/or showing early ageing of the skin."
Even if a claim does recite a law of nature or natural phenomenon, it may still be eligible. See MPEP 2106.04. For example, claims reciting a naturally occurring relationship between a patient’s genotype and the risk of QTc prolongation (a law of nature) were held eligible as not "directed to" that relationship because they also recited a step of treating the patient with an amount of a particular medication that was tailored to the patient’s genotype. Vanda Pharms., 887 F.3d at 1134-36, 126 USPQ2d at 1279-81.
In this instant claim, however, the administering step of claim 23 does not render the claim patent-eligible under 35 U.S.C. 101 because the treating step with a cosmetic composition is broadly recited and it not tailored to the subject's fungal composition. The specification describes "cosmetic composition used in the treatment method of the invention comprises probiotics and/or prebiotics, in particular enabling promoting the presence of commensal flora" (page 9, lines 20-21), but this composition comprising probiotics and/or prebiotics is not indicated to treat the fungal composition naturally correlating with the early skin ageing phenotype.
The rest of dependent claims also do not recite additional elements that amount to significantly more than the judicial exception, as they represent mere general linkage of the judicial exception to the additional elements in the claims (MPEP § 2106.05(h)).
In conclusion, the claims are not patent eligible under 35 U.S.C. 101.
Repones to Arguments
Applicant's arguments below have been fully considered but are not found persuasive.
"Claims 1-2 and 4-22 are rejected under 35 U.S.C. § 101. Independent claim 1, as
amended, and claims dependent thereon are not merely directed to a law of nature of nature without significantly more. The invention has a practical application beyond the simple law of nature. This is further emphasized by new claim 23, adding a step of treating the subject showing signs of skin aging to the method of claim 1.
Also, with respect to the question of patentability under 3 5 USC § 101, please keep in mind as stated in Mayo Collaborative Servs. v. Prometheus Labs., Inc., 566 U.S. 66 (2012), the limited purpose for the exceptions is to protect the "basic tools of scientific and technological work." The Supreme Court in Mayo emphasized that there must be some balance in the application of the exclusionary rule in stating" .. . too broad an interpretation of this exclusionary principle could eviscerate patent law. For all inventions at some level embody, use, reflect, rest upon, or apply laws of nature, natural phenomena, or abstract ideas." Furthermore, in Diamondv. Chakrabarty, 447 US 303,206 USPQ 193 the Supreme Court stated that " ... Congress intended statutory subject matter to 'include anything under the sun that is made by man'." In addition, the written description of the application should be considered since such helps to provide an understanding of the claims. Please see Chamberlain Grp., Inc. v. Techtronic Indus. Co., 935 F. 3d 1341, 1346 (Fed. Cir. 2019).
Furthermore, even if a claim involves a law of nature or an abstract concept, it is not necessarily rendered patent ineligible. Please see Alice Corp. Pty. Ltd v. CLS Bank, Int 'l, 573 U.S. 208,217, 110 USPQ2d 1976, 1980-81 (2014) and Gottschalk v. Benson, 409 U.S. 63, 67 (1972).
Also, of interest is the Statement by Director Squires before the United States Senate Subcommittee on Intellectual Property Committee on the Judiciary dated October 10, 2025 ( copy enclosed). " (Remarks, page 9-10)
These arguments are not persuasive.
The requirements for a proper response to a rejection may be found in 37 CFR 1.111(b) and MPEP §714.02; see also MPEP §707.07(a). The reply by the applicant or patent owner must be reduced to a writing which distinctly and specifically points out the supposed errors in the examiner's action and must reply to every ground of objection and rejection in the prior Office action.
Here, the remarks do not consider the specific ground of rejection in the prior rejection. Applicant asserts practical application in view of newly added claim 23, reciting a treating step, however, the remarks do not provide any specific reasons as to why either the findings of fact or the legal conclusion of patent ineligibility for independent claim 1 ꟷ which does not recite any treating step ꟷ is allegedly in error.
The legal decisions cited discuss various aspects of subject matter eligibility but the arguments make only generalizations not tied to the facts of the instant case. Thus, the remarks in response to the anticipation rejection do not comply with 37 CFR 1.111(b) and MPEP § 714.02. However, Applicant’s reply is considered to be a bona fide attempt at a response and is being accepted as a complete response.
Claim Rejections - 35 USC § 102 -- New Grounds
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.
The following are new grounds of rejections necessitated by Applicant's amendments. Although the claims were previously rejected as being unpatentable over the same reference(s), Applicant's amendments have necessitated the inclusion of new grounds of rejections in this Office action.
Claims 1-2, 4-5, 8, 11 and 21-22 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Turin (Turin et al. Fast, simple and highly sensitive double-rounded polymerase chain reaction assay to detect medically relevant fungi in dermatological specimens. Eur J Clin Invest. 2000;30:511–8), as evidenced by
Khalid (Khalid et al. Candida Fungus Skin Infection; healthline.com; Published on July 18, 2012 ; web.archive.org/web/20140221002013/http://www.healthline.com/health/skin/candida-fungus#Symptoms) and
Haleem (Haleem et al. Fungal pollution of indoor environments and its management. Saudi J Biol Sci. 2012 Oct;19(4):405-26. doi: 10.1016/j.sjbs.2012.06.002. Epub 2012 Jun 15. PMID: 23961203; PMCID: PMC3730554).
Regarding claim 1, Turin teaches a diagnosis method comprising:
a step (a) of determining in a skin sample of the subject the level of a first marker of fungi comprising a nucleic acid encoding an ITS 1(< Internal Transcribed Spacer 1 >) region of sequence at least 90 % identical to sequence SEQ ID NO: 1 (Table 1; Figure 2, according to specification, page 9, a fungi comprising SEQ ID NO: 1 is any fungi in the genus Candida, e.g. Candida albicans in Figure 2).
As the body of claim 1 only requires a single step determining level of ITS1 of SEQ ID NO: 1 in a skin sample, any prior art reference which teaches to merely detect ITS1 levels in a skin sample will meet claim 1.
Regarding claim 2, Turin teaches said first marker is selected from the group constituted of fungi of genus Candida (Table 1; Figure 2, Candida albicans).
Regarding claims 4 and 11, Turin teaches
(b) comparing the level of the first marker measured at step (a) with a control (Figure 2, lane 24 is negative control; lane 7 is Candida albicans); and
(c) on the basis of the comparison at step (b), determining whether the skin of the subject shows early ageing (Table 2, Patient # 10 tested positive for Candida infection per PCR).
While Turin does not explicitly teach determining whether a subject's skin shows early ageing, it teaches this limitation by teaching the determination of Candida infection, which has rashes, or areas of red patches as a known symptom, as evidenced by Khalid (entire document). Candida infection qualifies as early aging of the skin, as the claims defines early aging as encompassing skin conditions exhibiting red patches.
The claims and the specification describe early aging as encompassing a high abundance of Candida fungi on the skin (specification, page 7, lines 26-30 for example) , red patches, and other common signs of aging. Therefore, any prior art that teaches a correlation between the claimed ITS1 sequence and any of these conditions would fall within the scope of the claims.
Regarding claim 5, Turin teaches the level of the first marker is determined by measuring the level of the corresponding ITS1 DNA sequence region(Table 1; Figure 2).
Regarding claim 8, Turin teaches the early ageing of the skin is pollution-related by teaching Candida infection (Table 2), which is a skin condition that relate to indoor pollution, as evidenced by Haleem (page 414, left hand col, para 2, lines 5-7).
Regarding claim 21, Turin teaches method further comprises determining the level of at least one marker selected from the group consisting of fungi comprising a nucleic acid encoding an ITS 1 region of sequence at least 90 % identical to sequence SEQ ID NO: 3 (Table 1; Figure 2, Aspergillus sp. is inherently a fungi comprising SEQ ID NO: 3 according to Application's specification: page 4: "Sequence SEQ ID NO: 3 is a sequence representative of the ITS1 of fungi of genus Emericella"; page 5 "By « fungi of genus Emericella », it is meant herein teleomorphs of fungi of genus Aspergillus.").
Regarding claim 22, Turin teaches fungi of genus Emericella (Table 1; Figure 2, Aspergillus sp. is inherently a fungi comprising SEQ ID NO: 3 according to Application's specification: page 4: "Sequence SEQ ID NO: 3 is a sequence representative of the ITS1 of fungi of genus Emericella"; page 5 "By « fungi of genus Emericella », it is meant herein teleomorphs of fungi of genus Aspergillus.").
Claim Rejections - 35 USC § 103 -- New Grounds
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.
Claims 6-7, 9, 13, 15-16, 18-20 and 24 are rejected under 35 U.S.C. 103 as being unpatentable over Turin (Turin et al. Fast, simple and highly sensitive double-rounded polymerase chain reaction assay to detect medically relevant fungi in dermatological specimens. Eur J Clin Invest. 2000;30:511–8), in view of
Leung (Leung et al. (2016). Skin fungal community and its correlation with bacterial community of urban Chinese individuals. Microbiome, 4, Article 46. doi.org/10.1186/s40168-016-0192-z).
A) The teachings of Turin are recited above and applied as for base claims 1 and 5.
Turin teaches methods of detecting medically relevant fungi in dermatological samples (entire document).
Regarding claim 6, while Turin teaches PCR amplification of the ITS1 region (entire document, table 1 for example), it does not explicitly teach sequencing.
B) Leung teaches a method for analyzing skin fungal community using PCR and sequencing (entire document, methods for example).
Regarding claim 6, Leung teaches PCR amplification of the ITS1 region, followed by sequencing the amplicons (page 3, left-hand col, para 2 “PCR, sequence library preparation, and sequencing”).
C) It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to apply the sequencing approach taught by Leung in the method of Turin. Both references are in the same field of analyzing nucleic acids for identifying and characterizing fungi on the skin, and Leung provides a sequencing approach as a logical and predictable extension of the PCR method taught by Turin. The combination of Turin and Leung represents an obvious, predictable use of prior art elements(i.e. sequencing of PCR amplicons) according to a known method (i.e. analyzing skin fungi by PCR amplification) to yield predictable results (i.e. analyzing fungal taxonomy at large-scale via sequencing). (See MPEP §2143)
C) Regarding claims 7, 16 and 18-20, Leung teaches before PCR, taking a skin sample by rubbing the surface of the skin of the subject(page 2, right hand col, lines 33-35).
Regarding claim 9, Leung teaches the subject's age is between 25 and 45 (Additional file 5: Figure S1, age group 21-50).
Regarding claims 13 and 15, Leung teaches measuring the relative abundance of the corresponding ITS1 DNA sequence (page 5, right-hand col, lines 4-7).
Regarding claim 24, Leung teaches a reference value determined by the mean value of the level of the marker(s) in a determined population (page 6, right-hand col, para 2, lines 2-5, mean BCD (measures fungal composition) is compared between groups of individuals).
Claim 23 is rejected under 35 U.S.C. 103 as being unpatentable over Turin (Turin et al. Fast, simple and highly sensitive double-rounded polymerase chain reaction assay to detect medically relevant fungi in dermatological specimens. Eur J Clin Invest. 2000;30:511–8), in view of Wei et al. (CN103462881B - A kind of composition and method of making the same promoting skin microecological balance; Published on 2016-06-22; hereinafter “Wei”; references are made to the attached copy with English translation),
as evidenced by Khalid (Khalid et al. Candida Fungus Skin Infection; healthline.com; Published on July 18, 2012.
A) The teachings of Turin are recited above and applied as for base claim 1.
Turin teaches methods of detecting medically relevant fungi in dermatological samples (entire document).
Turin teaches the determination of Candida infection (Table 2, Patient # 10 tested positive for Candida infection per PCR), which has rashes, or areas of red patches as a known symptom, as evidenced by Khalid (entire document).
Candida infection qualifies as early aging of the skin, as the claims defines early aging as encompassing skin conditions exhibiting red patches. Therefore, Turin teaches diagnosing a subject as showing early ageing of the skin.
However, Turin does not explicitly disclose treating the skin of the subject diagnosed as showing early ageing of the skin with a cosmetic composition allowing reducing and/or showing early ageing of the skin.
B) Wei teaches a cosmetic composition particularly suitable for daily treatment of facial skin for bacteria flora imbalance (entire document, [0119] for example).
Wei teaches the bacteria flora imbalance in the skin microecosystem is indicated by the disruption of the balance between probiotic bacteria and harmful and invasive flora ([0005]), such harmful flora to the skin include Candida albicans, which causes aging ([0004] line 7). Such bacteria flora imbalance could lead to stress reactions such as infection, inflammation, red swelling, pruritus, scars, erythema and the like, thereby losing the original luster of the skin, causing more skin problems and even causing skin aging. ([0005]).
Regarding claim 1, Wei teaches its composition has multiple beneficial effects such as astringency, nourishing, whitening of the skin, delaying skin aging while promoting the growth of skin probiotics ([0117]); specifically, subjects show reduced red patches of the skin after treatment with the composition ([0150]1 lines 1-3). Therefore, Wei's composition allows for the reducing and slowing of early ageing of the skin.
C) It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to apply the composition disclosed in Wei, which treats bacterial flora imbalance in the skin micro-ecosystem, to the method of diagnosing skin infection taught by Turin. Both references are within the same field of studying the skin microbiome and its relation to skin conditions. Turin discusses Candida infection, which causes skin conditions characterized by red patches. Wei describes a composition that effectively treats skin redness and specifically highlights its ability to address bacterial flora imbalances caused by harmful flora, such as Candida albicans.
The person of ordinary skill would have had a reasonable expectation of success in combining these teachings because the references provide complementary teachings. In light of the teachings in Wei, Candida infection, as determined in Turin, is an over population of the Candida yeasts, thus indicating a disruption in the balance in the skin microbiome. Therefore, using a composition suitable for treating such imbalance is a logical next step.
The skilled artisan would have been motivated to combine the teachings of these references to leverage the potential benefits of the composition described in Wei, such as delaying skin aging while promoting the growth of skin probiotics.
Conclusion
No claims are 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 TIAN NMN YU whose telephone number is (703)756-4694. The examiner can normally be reached Monday - Friday 8:30 am - 5:30 pm.
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/TIAN NMN YU/Examiner , Art Unit 1681 /AARON A PRIEST/Primary Examiner, Art Unit 1681
1 Acne is commonly known as having the phenotype of red patches on the skin, see universaldermatology.com/identifying-21-common-red-spots-on-skin/