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 Status
Claims 1 & 11-15 filed on 07/15/2026 are pending. Claims 4-9 are withdrawn from consideration as being drawn to a non-elected invention. Claim 1 is currently under examination directed to the elected species of DSG4 (see response dated 01/12/2026). The cancellation of claims 2, 3, and 10 without prejudice or disclaimer and the newly added claims 11-15 in the reply filed on 07/15/2026 is acknowledged. All the amendments and arguments have been thoroughly reviewed but are deemed insufficient to place this application in condition for allowance. The following rejections are either newly applied, as necessitated by amendment, or are reiterated. They constitute the complete set being presently applied to the instant application. Response to Applicant’s argument follow. This action is FINAL.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office Action.
Any rejection not reiterated is hereby withdrawn in view of the amendments to the claims.
Information Disclosure Statement
Only the abstract of the reference in the IDS submitted on 07/15/2026, under the foreign patent documents section, was considered because an English copy of the full documents was not provided.
Claim Rejections - 35 USC § 112
Claims 1 & 11-15 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.
Regarding amended claim 1, the claim recites the limitation “said subject” in line 4 of the claim and there is insufficient antecedent basis for this limitation in the claim and it is unclear if “said subject” is meant to refer back to “a human subject” in lined 2 of claim 1.
Claims 11-15 are rejected due to their dependence on claim 1.
Claim Rejections - 35 USC § 101
Claims 1 & 11-15 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural correlation/law of nature and an abstract idea without significantly more. This judicial exception is not integrated into a practical application and the claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception for the reasons set forth below.
35 U.S.C. § 101 requires that to be patent-eligible, an invention (1) must be directed to one of the four statutory categories, and (2) must not be wholly directed to subject matter encompassing a judicially recognized exception. M.P.E.P. § 2106. Regarding judicial exceptions, “[p]henomena of nature, though just discovered, mental processes, and abstract intellectual concepts are not patentable, as they are the basic tools of scientific and technological work.” Gottschalk v. Benson, 409 U.S. 63, 67 (1972); see also M.P.E.P. § 2106. The unpatentability of abstract ideas was confirmed by the U.S. Supreme court in Bilski v. Kappos, 561 U.S. 593, 601 (June 28, 2010) and Alice Corp. Pty. Ltd. v. CLS Bank Int’l, 134 S. Ct. 2347, 2354 (2014). See also Myriad v Ambry, CAFC 2014-1361, -1366, December 17, 2014. The unpatentability of laws of nature was confirmed by the U.S. Supreme Court in Mayo Collaborative Services v. Prometheus Laboratories, Inc., 566 U.S. 66, 71 (2012). “[L]aws of nature, natural phenomena, and abstract ideas” are not patentable. Dia-mond v. Diehr, 450 U. S. 175, 185 (1981); see also Bilski v. Kappos, 561 U. S. at 601 (2010).
Claims Analysis:
As set forth in MPEP 2106, the claims have been analyzed to determine whether they are directed to one of the four statutory categories (STEP 1).
The instant claims are directed to methods and therefore are directed to one of the four statutory categories of invention.
The claims are then analyzed to determine if they recite a judicial exception (JE) (STEP 2A, prong 1) [Mayo Collaborative Services v. Prometheus Labs., Inc., 132 S. Ct. 1289, 1293 (2012), Alice Corp. Pry. Ltd. v. CLS Bank Int'l, 134 S. Ct. 2347 (2014)].
The claimed invention recites a method for in vitro prognosis and/or diagnosis of a common alopecic state of a scalp of androgenetic alopecia in a subject comprising measuring the level of at least one gene selected from a group and comparing with a control. This recitation is a natural correlation between expression level of at least one gene and prognosis and/or diagnosis of a common alopecic state of androgenetic alopecia. With regard to the natural correlation, as in Mayo, the relationship is itself a natural process that exists apart from any human action. The claimed invention also recites “comparing the level of at least one gene measuring in step a) with a control” and “determining whether the scalp of said subject exhibits a common alopecic state” which is a recitation of an abstract idea because it encompasses conclusions and determinations which can occur entirely within the mind. It is therefore determined that the claims are directed to judicial exceptions.
The claims are then analyzed to determine whether they recite an element or step that integrates the JE into a practical application (STEP 2A, prong 2) [Vanda Pharmaceuticals Inc., v. West-Ward Pharmaceuticals, 887 F.3d 1117 (Fed. Cir. 2018)].
The claims recite steps of measuring the expression level of at least one gene selected from a group, comparing the level with a control, and determining whether the scalp of said subject exhibits a common alopecic state of androgenetic alopecia, however this does not integrate the JE into a practical application because it is a mere data gathering step to use the correlation and does not add a meaningful limitation to the method.
In the absence of steps or elements that integrate the JE into a practical application, the additional elements/steps are considered to determine whether they add significantly more to the JE either individually or as an ordered combination, to “’transform the nature of the claim’ into a patent eligible application” [Mayo Collaborative Services v. Prometheus Labs., Inc., 132 S. Ct. 1289, 1293 (2012), Alice Corp. Pry. Ltd. v. CLS Bank Int'l, 134 S. Ct. 2347 (2014)] (STEP 2B).
In the instant situation, the steps of detecting the expression level of at least one gene, comparing the level with a control, and determining whether the scalp of said subject exhibits a common alopecic state of androgenetic alopecia, are generally recited and do not provide any particular reagents that might be considered elements that transform the nature of the claims into a patent eligible application because no specific elements/steps are recited. This step is not only a mere data gathering step, but the general recitation of detection of known nucleic acids is well understood, routine, and conventional activity (See MPEP 2106.05(d)(II)). Applicant is reminded that in Mayo, the Court found that “[i]f a law of nature is not patentable, then neither is a process reciting a law of nature, unless that process has additional features that provide practical assurance that the process is more than a drafting effort designed to monopolize the law of nature itself." Further "conventional or obvious" "[pre]solution activity" is normally not sufficient to transform an unpatentable law of nature into a patent-eligible application of such a law”. Flook, 437 U. S., at 590; see also Bilski, 561 U. S., at ___ (slip op., at 14) (“[T]he prohibition against patenting abstract ideas ‘cannot be circumvented by’ . . . adding ‘insignificant post-solution activity’” (quoting Diehr, supra, at 191–192)). The Court also summarized their holding by stating “[t]o put the matter more succinctly, the claims inform a relevant audience about certain laws of nature; any additional steps consist of well understood, routine, conventional activity already engaged in by the scientific community; and those steps, when viewed as a whole, add nothing significant beyond the sum of their parts taken separately.” Therefore these limitations/steps do not “‘transform the nature of the claim’ into a patent-eligible application.’” Alice, 134 S. Ct. at 2355 (quoting Mayo, 132 S. Ct. at 1297).
When viewed as an ordered combination, the claimed limitations are directed to nothing more than the determination that a natural correlation/phenomena exists. Any additional element consists of using well understood, routine and conventional activity, and those steps, when viewed as a whole, add nothing significant beyond the sum of their parts taken separately.
Accordingly, it is determined that the instant claims are not directed to patent eligible subject matter.
Response to Arguments
The response traverses the rejection. The response asserts that as amended claim 1 is directed to a specific in vitro diagnostic method through measurement of expression levels of a specifically recited group of intercellular-junction genes and the claim further requires determining that the scalp exhibits androgenetic alopecia when the measure expression level is decreased relative to a control level and claim 1 therefore recites a specific laboratory-based diagnostic application and not merely a natural phenomenon itself. Further, the response asserts that even though the claimed invention involves a biological relationship between decreased expression of the recited genes and androgenetic alopecia, independent claim 1 is not directed to that relationship in the abstract and that the claims requires obtaining and analyzing a biological sample, measuring expression levels of specifically recited biomarkers, comparing the expression level with a control, and using those measurements to generate a clinically meaningful diagnostic result and that such a claim is integrated into a practical application and therefore satisfies Step 2A, Prong Two of the USPTO eligibility framework. This argument has been thoroughly reviewed but was not found persuasive as the claims recite steps of measuring the expression level of at least one gene selected from a group, comparing the level with a control, and determining whether the scalp of said subject exhibits a common alopecic state of androgenetic alopecia, however this does not integrate the JE into a practical application because it is a mere data gathering step to use the correlation and does not add a meaningful limitation to the method.
The response also asserts that the claimed measurement is not insignificant pre-solution activity and that the diagnostic information required by the claim does not exist until expression levels of the recited genes are measured in a biological sample and the claimed method therefore requires a physical laboratory procedure that generates information used to diagnose androgenetic alopecia. Further, the response asserts that the claimed determination cannot be performed without first obtaining laboratory-generated gene-expression measurements from the biological sample and the claim therefore requires more than a mere observation or mental evaluation of existing information. This argument has been thoroughly reviewed but was not found persuasive. First, while the claims recite steps of measuring the expression level of at least one gene selected from a group, comparing the level with a control, and determining whether the scalp of said subject exhibits a common alopecic state of androgenetic alopecia, this does not integrate the JE into a practical application because it is a mere data gathering step to use the correlation and does not add a meaningful limitation to the method. Second, mental processes, concepts performed in the human mind, such as observation, evaluation, judgment, and opinion are directed towards abstract ideas (see MPEP 2106.04(a)(3)).
The response also asserts that no evidence is provided that the claimed combination of measuring expression of the specifically recited intercellular-junction genes and diagnosing androgenetic alopecia based on decreased expression levels was well-understood, routine, and conventional. This argument has been thoroughly reviewed but was not found persuasive. First, the steps of detecting the expression level of at least one gene, comparing the level with a control, and determining whether the scalp of said subject exhibits a common alopecic state of androgenetic alopecia, are generally recited and do not provide any particular reagents that might be considered elements that transform the nature of the claims into a patent eligible application because no specific elements/steps are recited. This analysis holds for generally recited limitations drawn to protocols and sample types. This step is not only a mere data gathering step, but the general recitation of detection of known nucleic acids is well understood, routine, and conventional activity (See MPEP 2106.05(d)(II)). Therefore, when viewed as an ordered combination, the claimed limitations are directed to nothing more than the determination that a natural correlation/phenomena exists. Any additional element consists of using well understood, routine and conventional activity, and those steps, when viewed as a whole, add nothing significant beyond the sum of their parts taken separately.
The response also asserts that claim 1 is limited to androgenetic alopecia and to a specifically recited set of intercellular-junction genes and claim 1 therefore represents a particularized diagnostic application rather than an attempt to monopolize a natural law. This argument has been thoroughly reviewed but was not found persuasive as monopolization of a natural law is not a standard for determination of patent eligibility under 35 U.S.C. 101.
For these reasons, and the reasons already made of record and modified to address the claims as currently amended, the rejections are maintained and applied to the newly amended claims.
Claim Rejections - 35 USC § 103
Claim(s) 1 & 11-15 is/are rejected under 35 U.S.C. 103 as being unpatentable over Nagasawa (Nagasawa et al.; Dermatol Ther, Vol. 6, pages 59-68, February 2016), in view of Owens (Owens et al.; Developmental Biology, Vol. 322, pages 156-166, July 2008).
Regarding amended claim 1, Nagasawa teaches a method of measuring desmoglein expression, comprising expression of DSG4 in human subjects with androgenetic alopecia compared with a control (abstract methods lines 1-3 & 14-16; pg. 60 column 1 1st full paragraph lines 1-21; pg. 60-61 paragraph bridging pg. 60 & 61 lines 8-13; pg. 62 paragraph bridging column 1 & 2 lines 19-34; Fig. 5).
Nagasawa does not teach determining the scalp exhibits a common alopecia state when the expression level of DSG4 is decreased compared to a control level.
Owens teaches examining the expression levels of key molecules associated with hair follicle differentiation in progressive alopecia (common alopecic state comprising androgenetic alopecia) in which DSG4 is downregulated (decreased) in samples that develop progressive alopecia (common alopecic state comprising androgenetic alopecia) compared to control (determining the scalp exhibits a common alopecic state comprising androgenetic alopecia when the expression level of DSG4 is decreased compared to a control level) (abstract lines 1-6; pg. 157 column 2 1st full paragraph lines 1-11; pg. 157 column 2 2nd full paragraph lines 11-14; pg. 162 column 1 1st full paragraph lines 21-33; pg. 162-163 paragraph bridging pg. 162 & 163 lines 1-6; Fig. 3; Fig. 4). Owens also teaches that this methods indicates the importance of identifying functional Smad transcriptional targets, comprising DSG4, in different developmental stages to identify targets in hair differentiation leading to progressive alopecia comprising androgenetic alopecia (pg. 162 column 1 1st full paragraph lines 21-33; pg. 165 column 1 1st full paragraph lines 1-8; pg. 165 column 2 1st full paragraph lines 1-14).
Nagasawa and Owens are considered to be analogous to the claimed invention because they are all in the same field of measuring expression of genes in common progressive alopecic states. Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of measuring the expression level of DSG4 in samples from a human subject with androgenetic alopecia in Nagasawa to incorporate determining the scalp exhibits a common alopecic state when the expression level of DSG4 is decreased compared to a control level as taught in Owens because Owens teaches that doing so would provide a method of identifying functional Smad transcriptional targets, comprising DSG4, in different developmental stages to identify targets in hair differentiation leading to progressive alopecia.
Regarding new claim 11, Nagasawa teaches a method of measuring desmoglein expression, comprising expression of DSG4 in human subjects with androgenetic alopecia (abstract methods lines 14-16; pg. 60 column 1 1st full paragraph lines 1-21; pg. 62 paragraph bridging column 1 & 2 lines 19-34; Fig. 5).
Owens teaches examining the expression levels of key molecules associated with hair follicle differentiation in progressive alopecia (common alopecic state comprising androgenetic alopecia) comprising measuring DSG4 expression levels in samples that develop progressive alopecia (common alopecic state comprising androgenetic alopecia) (abstract lines 1-6; pg. 157 column 2 1st full paragraph lines 1-11; pg. 157 column 2 2nd full paragraph lines 11-14; pg. 162 column 1 1st full paragraph lines 21-33; pg. 162-163 paragraph bridging pg. 162 & 163 lines 1-6; Fig. 3; Fig. 4).
Regarding new claim 12, Owens teaches that DSG4 mRNA expression levels were measured (the expression level corresponds to the concentration or amount of the mRNA expression product encoded by said at least one gene) (pg. 157-158 paragraph bridging pg. 157 & 158 lines 26-27; pg. 162-163 paragraph bridging pg. 162 & 163 lines 1-3).
Regarding new claim 13, Nagasawa teaches a method of measuring desmoglein expression, comprising expression of DSG4 in human subjects with androgenetic alopecia (abstract methods lines 14-16; pg. 60 column 1 1st full paragraph lines 1-21; pg. 62 paragraph bridging column 1 & 2 lines 19-34; Fig. 5).
Owens teaches examining the expression levels of key molecules associated with hair follicle differentiation in progressive alopecia (common alopecic state comprising androgenetic alopecia) comprising measuring DSG4 expression levels in samples that develop progressive alopecia (common alopecic state comprising androgenetic alopecia) (abstract lines 1-6; pg. 157 column 2 1st full paragraph lines 1-11; pg. 157 column 2 2nd full paragraph lines 11-14; pg. 162 column 1 1st full paragraph lines 21-33; pg. 162-163 paragraph bridging pg. 162 & 163 lines 1-6; Fig. 3; Fig. 4).
Regarding new claim 14, Owens teaches that DSG4 mRNA expression levels were measured (the expression level corresponds to the concentration or amount of the mRNA expression product encoded by said at least one gene) (pg. 157-158 paragraph bridging pg. 157 & 158 lines 26-27; pg. 162-163 paragraph bridging pg. 162 & 163 lines 1-3).
Regarding new claim 15, Owens teaches that DSG4 mRNA expression levels were measured (the expression level corresponds to the concentration or amount of the mRNA expression product encoded by said at least one gene) (pg. 157-158 paragraph bridging pg. 157 & 158 lines 26-27; pg. 162-163 paragraph bridging pg. 162 & 163 lines 1-3).
Response to Arguments
The response traverses the rejection. The response asserts that amended claim 1 is expressly limited to a method for the prognosis and/or diagnosis of androgenetic alopecia and Owens does not expressly or inherently disclose androgenetic alopecia and that the progressive alopecia observed in Smad4 knockout mouse model is not the same as or not to be equated to androgenetic alopecia as no specified in independent claim 1. Further, the response asserts that claim 1 is directed to an in vitro prognosis and/or diagnosis method performed on a biological sample and that Owens does not disclose obtaining a biological sample from a subject for diagnostic or prognostic evaluation and therefore Owens does not disclose the claimed diagnostic context or diagnosing androgenetic alopecia on the basis of decreased DAG4 expression (it is noted that the applicant’s response also discusses Christiano, however Christiano is no longer applied in prior art rejections of the claims and therefore will not be further discussed in the response to arguments). These arguments have been thoroughly reviewed but were not found persuasive. First, applicant’s arguments rely on language solely recited in preamble recitations in claim(s) 1. When reading the preamble in the context of the entire claim, the recitation "for the in vitro prognosis and/or diagnosis of a common alopecic state" is not limiting because the body of the claim describes a complete invention and the language recited solely in the preamble does not provide any distinct definition of any of the claimed invention’s limitations. Thus, the preamble of the claim(s) is not considered a limitation and is of no significance to claim construction. See Pitney Bowes, Inc. v. Hewlett-Packard Co., 182 F.3d 1298, 1305, 51 USPQ2d 1161, 1165 (Fed. Cir. 1999). See MPEP § 2111.02. Further, the claims recite the limitation of “determining that the scalp exhibits a common alopecic state when the expression level of at least one gene … measure in step a) is decreased compared to a control level” and, as discussed further above, Owens teaches examining the expression levels of key molecules associated with hair follicle differentiation in progressive alopecia (common alopecic state comprising androgenetic alopecia) in which DSG4 is downregulated (decreased) in samples that develop progressive alopecia (common alopecic state comprising androgenetic alopecia) compared to control (determining the scalp exhibits a common alopecic state comprising androgenetic alopecia when the expression level of DSG4 is decreased compared to a control level) (abstract lines 1-6; pg. 157 column 2 1st full paragraph lines 1-11; pg. 157 column 2 2nd full paragraph lines 11-14; pg. 162 column 1 1st full paragraph lines 21-33; pg. 162-163 paragraph bridging pg. 162 & 163 lines 1-6; Fig. 3; Fig. 4). Second, the combination of Nagasawa and Owens, as applied to claim 1 as necessitated by amendment, teach all of the limitations of currently pending claim 1 as discussed further above. Further, it is noted that androgenetic alopecia is a form of progressive alopecia as further taught by Nagasawa that teaches that androgenetic alopecia is characterized by recession of the frontal hairline and hair loss that is associated with progressive miniaturization and loss of hair follicles (pg. 59-60 paragraph bridging pg. 59 & 60 lines 1-9 of Nagasawa).
The response also asserts that the combination of Christiano and Owens would not teach or suggest the presently claimed method of diagnosing or prognosing androgenetic alopecia based upon decreased expression of a recited intercellular junction gene relative to a control. This argument has been thoroughly reviewed but was not found persuasive Christiano is no longer applied in prior art rejections of the claims and the combination of Nagasawa and Owens, as applied to claim 1 as necessitated by amendment, teach all of the limitations of currently pending claim 1 as discussed further above.
For these reasons, and the reasons already made of record and modified to address the claims as currently amended, the rejections are maintained and applied to the newly amended claims.
Conclusion
Claims 1 & 11-15 are rejected.
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 BAILEY C BUCHANAN whose telephone number is (703)756-1315. The examiner can normally be reached Monday-Friday 8:00am-5:00pm ET.
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/BAILEY BUCHANAN/Examiner, Art Unit 1682
/JEHANNE S SITTON/Primary Examiner, Art Unit 1682
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