DETAILED ACTION
Applicant’s response, filed 21 July 2025, has been fully considered. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Status of Claims
Claims 1-97 are cancelled.
Claims 106-108 are newly added.
Claims 98-108 are pending.
Claims 98-108 are rejected.
Priority
Applicant’s claim for the benefit of a prior-filed application, U.S. 13/881,576 and 15/466,141 under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged.
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application No. 13/881,576 and 15/466,141 , fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application for the same reasons discussed below regarding the rejection of claims 98-108 under pre-AIA 35 U.S.C. 112, first paragraph. That is, the Applications ‘576 and ‘141 do not provide support for the limitations of “the array is not a complete genome array” and “…the method does not comprise measuring the complete genome” as recited in claims 98-99, respectively, and claims dependent therefrom.
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
However, the certified copy of the foreign priority document filed in parent Application No. 13/881,576 similarly does not disclose the above limitation of claims 98-108.
Accordingly, the effective filing date of the claimed invention is 08 March 2021.
Claim Rejections - 35 USC § 112 (pre-AIA ), first paragraph
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.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
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 of carrying out his invention.
Claims 98-108 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) 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. This rejection is newly recited and necessitated by claim amendment.
Independent claims 98-99, and claims dependent therefrom, recite “An array…wherein the array is not a complete genome array” and “…said method comprising measuring…an expression of nucleic acid molecules…wherein the method does not comprise measuring the complete genome”, respectively. Dependent claim 108 also recites “…the array is not a complete genome array”. Independent claims 98 and 99 and dependent claim 108 require the array includes binding moieties for and measure expression for, 11 specific biomarkers including SQLE, TAS2R5, KGFLP1/2, TAPT1, SPRY2, FASN, BCL7A, SLC25A32, FTHP1, ATP6V1H, and HIST1H1E, respectively, and then places a negative limitation on the biomarkers being measured to exclude any arrays comprising the whole genome or the measuring the complete genome.
However, any negative limitation or exclusionary proviso must have basis in the original disclosure. If alternative elements are positively recited in the specification, they may be explicitly excluded in the claims. See In re Johnson, 558 F.2d 1008, 1019, 194 USPQ 187, 196 (CCPA 1977) ("[the] specification, having described the whole, necessarily described the part remaining."). See MPEP 2173.05(i). In this case, Applicant’s specification does not provide support for the above negative limitation for the following reasons.
First, Applicant’s remarks filed 21 July 20205 point to Applicant’s specification at pg. 3, lines 9-10 and pg. 31, lines 17-19 for support for using a whole-genome array, and remarks that therefore, there is a clear basis for specifically excluding complete genome arrays, given MPEP 2174.015(i) states if alternative embodiments are positively recited in the specification, they may be explicitly excluded in the claims. However, Applicant’s specification at pg. 3, lines 9-10 and pg. 31, lines 17-19 discloses a separate process in which the biomarker signature of 200 transcripts was identified by analyzing ROC curves of genome-wide biomarkers from a whole-genome array. This is in contrast to the disclosure of the array used to predict whether an agent induces sensitization of human skin, including an array that comprises one or more binding moieties from the 200 gene signature. For example, Applicant’s specification discloses the binding array is capable of binding to all of the biomarkers in Table 3A and 3B and further discloses “an analytical kit…consisting of: A) an array according to the second aspect of the invention”. The portions of Applicant’s specification cited by Applicant corresponding to a whole-genome array are clearly not disclosed as alternative elements/arrays for identifying agents capable of inducing skin sensitization, and instead are disclosed for identifying biomarkers capable of identifying agents capable of inducing skin sensitization. Therefore, Applicant’s specification does provide support for an array comprising or consisting of binding moieties for the 200 biomarkers of the signature. However, this does not provide support for the broader, more generic invention of an array including binding moieties of, or measuring, only 11 of the 200 biomarkers (the recited biomarkers i)-xi)), but further including binding moieties of or measuring any other biomarkers and specifically excluding an embodiment in which the biomarkers don’t encompass a complete genome. See MPEP 2163 II. B.
For the reasons discussed above, the specification does not provide a sufficient disclosure of the limitations discussed above recited in claims 98-108 to demonstrate to one of ordinary skill in the art that the inventor possessed the invention at the time the application was filed. THS IS A NEW MATTER REJECTION. For more information regarding the written description requirement, see MPEP §2161.01- §2163.07(b).
Response to Arguments
Applicant's arguments filed 21 July 2025 regarding 35 U.S.C. 112(pre-AIA ), first paragraph or 112(a) have been fully considered but they are not persuasive.
Applicant remarks the specification discloses the use of a complete genome array at pg. 3, lines 9-10 and pg. 31, lines 17-19, but further teaches biomarker signatures of 200 or fewer markers which can be utilized, and as such, there is clear basis for specifically excluding complete genome arrays, and having described the whole, Applicant has necessarily described the part remaining after the exclusion of a member (Applicant’s remarks at pg. 6, para. 7 to pg. 7, para. 4). Applicant remarks that because the claims were amended to remove the reference to a maximum of 200 biomarkers, the rejection should be withdrawn (Applicant’s remarks at pg. 7, para. 5 to pg. 8, para. 3).
This argument is not persuasive. Any negative limitation or exclusionary proviso must have basis in the original disclosure. If alternative elements are positively recited in the specification, they may be explicitly excluded in the claims. See In re Johnson, 558 F.2d 1008, 1019, 194 USPQ 187, 196 (CCPA 1977) ("[the] specification, having described the whole, necessarily described the part remaining."). See also Ex parte Grasselli, 231 USPQ 393 (Bd. App. 1983), aff’d mem., 738 F.2d 453 (Fed. Cir. 1984). In describing alternative features, the applicant need not articulate advantages or disadvantages of each feature in order to later exclude the alternative features. See Inphi Corporation v. Netlist, Inc., 805 F.3d 1350, 1356-57, 116 USPQ2d 2006, 2010-11 (Fed. Cir. 2015).
While Applicant points to pg. 3, lines 9-10, lines 17-19 of the specification for disclosure of an alternative element/feature of whole-genome arrays, these portions of the specification only disclose the process in which the biomarker signature of 200 transcripts was identified by analyzing ROC curves of genome-wide biomarkers from a whole-genome array. That is, the specification does not describe a whole-genome array as an alternative to the disclosed array comprising or consisting of biomarkers from the 200 biomarker signature used for the identification of agents capable of inducing sensitization of human skin, and instead only uses a whole-genome array to analyze genes genome-wide to ultimately identify a biomarker signature. Therefore, these arrays are not disclosed as alternative elements that provide a basis for specifically excluding an embodiment that is a whole genome array from an array comprising or consisting of one or more biomarkers from the 200 biomarker signature.
This is in contrast to a theoretical disclosure that discussed that an array comprising one or more biomarkers from the 200 biomarker signature or a whole genome array could be used for identifying agents capable of inducing sensitization. In this exemplary case, the specification clearly discloses the whole genome array as an alternative to the array of one or more biomarkers of the signature, such that the array of one or more biomarkers could exclude a whole genome array.
However, in this case, Applicant’s specification does not provide support for using any array including 11 biomarkers of the 200 biomarker signature, in addition to any combination of additional biomarkers so long as the biomarkers do not encompass a complete genome.
Claim Rejections - 35 USC § 112 (pre-AIA ), second paragraph
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 99-108 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. This rejection is newly recited and necessitated by claim amendment.
Claim 99, and claims dependent therefrom, are indefinite for recitation of “… the method does not comprise measuring the complete genome”. There is insufficient antecedent basis for this limitation in the claim because claim 99 does not previously recite a complete genome. Given there is more than one genome (e.g. human, rat, etc.), it is unclear which genome, “the complete genome” is referring to. For purpose of examination, the limitation will be interpreted to mean “a complete genome”.
Claim Rejections - 35 USC § 101
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 98-108 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a law of nature or natural phenomenon without significantly more. Any newly recited portion is necessitated by claim amendment.
The Supreme Court has established a two-step framework for this analysis, wherein a claim does not satisfy § 101 if (1) it is “directed to” a patent-ineligible concept, i.e., a law of nature, natural phenomenon, or abstract idea, and (2), if so, the particular elements of the claim, considered “both individually and as an ordered combination,” do not add enough to “transform the nature of the claim into a patent-eligible application.” Elec. Power Grp., LLC v. Alstom S.A., 830 F.3d 1350, 1353 (Fed. Cir. 2016) (quoting Alice, 134 S. Ct. at 2355). Applicant is also directed to MPEP 2106.
Step 1: The instantly claimed invention (claims 98-99 being representative) is directed a product and method for measuring biomarkers. Therefore, the instantly claimed invention falls into one of the four statutory categories. [Step 1: YES]
Step 2A: First it is determined in Prong One whether a claim recites a judicial exception, and if so, then it is determined in in Prong Two if the recited judicial exception is integrated into a practical application of that exception.
Step 2A, Prong 1: Under the MPEP § 2106.04, the Step 2A (Prong 1) analysis requires determining whether a claim recites an abstract idea, law of nature, or natural phenomenon.
Claim 98 recites the following natural product:
different binding moieties, wherein each different binding moiety selectively binds to a different nucleic acid molecule, and …comprising binding moieties selectively binding to nucleic acid molecules encoding each of the following biomarkers: squalene epoxidase (SQLE),ii) taste receptor, type 2, member 5 (TAS2R5),iii) keratinocyte growth factor-like protein 1/2/hypothetical protein FLJ20444 (KGFLP1/2),iv) transmembrane anterior posterior transformation 1 (TAPT1),v) sprouty homolog 2 (SPRY2),vi) fatty acid synthase (FASN),vii) B-cell CLL/lymphoma 7A (BCL7A),viii) solute carrier family 25, member 32 (SLC25A32),ix) ferritin, heavy polypeptide pseudogene 1 (FTHP1),x) ATPase, H+ transporting, lysosomal 50/57 kDa, V1 subunit H (ATP6V1H), andxi) his-tone cluster 1, H1e (HIST1H1E)…wherein [the different binding moieties are] not a complete genome;
Claim 99 recites the following limitation directed to a natural product:
…in a population of dendritic cells or a population of dendritic-like cells an expression of nucleic acid molecules encoding each of the following biomarkers: i) squalene epoxidase (SQLE),ii) taste receptor, type 2, member 5 (TAS2R5), iii) keratinocyte growth factor-like protein 1/2/hypothetical protein FLJ20444 (KGFLP1/2), iv) transmembrane anterior posterior transformation 1 (TAPT1),v) sprouty homolog 2 (SPRY2), vi) fatty acid synthase (FASN), vii) B-cell CLL/lymphoma 7A (BCL7A), viii) solute carrier family 25, member 32 (SLC25A32),ix) ferritin, heavy polypeptide pseudogene 1 (FTHP1), x) ATPase, H+ transporting, lysosomal 50/57 kDa, V1 subunit H (ATP6V1H), and xi) histone cluster 1, Hle (HISTIHIE), wherein the method does not comprise measuring the complete genome.
The identified claim limitations recite a law of nature or natural phenomenon for the following reasons. First, the various binding moieties of claim 98 that selectively bind to respective nucleic acid molecules encompass naturally occurring nucleic acids, including DNA or RNA, that bind to the respective biomarker, as described in Applicant’s specification at pg. 9, lines 1-11. This natural product is similar to the single-stranded DNA fragments known as "primers" identified as an example of laws of nature or natural phenomena in University of Utah Research Foundation v. Ambry Genetics Corp., 774 F.3d 755, 761, 113 USPQ2d 1241, 1244 (Fed. Cir. 2014). Furthermore, the binding moieties of claim 89 do not have any markedly different characteristics when compared to their naturally occurring counterpart on the respective nucleic acid of a naturally occurring gene to which they bind, again similar to the primers of University of Utah Research Foundation v. Ambry Genetics Corp. Overall, the binding moieties are the same as their naturally occurring counterpart, save for their location a and immobilization on an array. In Myriad, the Supreme Court made clear that not all changes in characteristics will rise to the level of a marked difference, e.g., the incidental changes resulting from isolation of a gene sequence are not enough to make the isolated gene markedly different. Myriad, 569 U.S. at 580, 106 USPQ2d at 1974-75. See MPEP 2106.04(c). Accordingly, the isolation of such naturally occurring sequences (binding moieties) and placement and immobilization on an array is not sufficient to provide a marked difference in characteristics, given the actual chemical and physical structure and form of the nucleic acids are unchanged. For example, arrays immobilize nucleic acids by placing nucleic acids onto charged substates, which do not require altering the structure or characteristics of the nucleic acid binding moieties relative to their natural counterparts. See Heise et al. (Immobilization of DNA on microarrays, 2006, Top Curr Chem, 261, pg. 1-25; newly cited), which reviews methods of immobilizing DNA on microarrays, including by using non-covalent coupling methods which rely on electrostatic bonds or van der Waals interactions to immobilize the DNA on a charged support (pg. 8, para. 1 through pg. 10; Fig. 8).
Regarding the method of claim 99, MPEP 2106.04(c) states in the limited situation where a process claim reciting a nature-based product is drafted in such a way that there is no difference in substance from a product claim, the claim is subject to the markedly different analysis for the recited nature-based product. These types of claims are drafted in a way that focuses on the product rather than the process steps. Here, claim 99 is directed to the expressed nucleic acid molecules encoding the recited genes (i.e. naturally occurring nucleic acid) within naturally occurring dendric cells or dendritic-like cells, and the existence and location of these expressed mRNA in cells is a natural phenomenon. This is similar to the example in MPEP 2106.04(c), which states claims to detecting naturally occurring cell-free fetal DNA (cffDNA) in maternal blood were held to be directed to the cffDNA, because the "existence and location of cffDNA is a natural phenomenon [and thus] identifying its presence was merely claiming the natural phenomena itself." Rapid Litig. Mgmt., 827 F.3d at 1048, 119 USPQ2d at 1374, (explaining the holding in Ariosa Diagnostics, Inc. v. Sequenom, 788 F.3d 1371, 115 USPQ2d 1152 (Fed. Cir. 2015)). Similar to the claims in Ariosa Diagnostics, Inc. v. Sequenom, the instant claims only identify the presence of (e.g. measure) a naturally occurring phenomena (the presence of expressed genes within dendritic cells).
Dependent claim 100 further recites a natural correlation between a test agent and the expression of biomarkers in dendritic cells, similar to the correlation that is the consequence of how a certain compound is metabolized by the body, identified in Mayo Collaborative Servs. v. Prometheus Labs., 566 U.S. 66, 75-77, 101 USPQ2d 1961, 1967-68 (2012). That is, the way in which a given test agent affects the expression of genes in dendritic cells is an entirely natural process. Dependent claim 100 also further limits the natural phenomena of the expressed nucleic acids to be within certain dendritic cells. Dependent claims 104-105 further limit the type of cell of the natural phenomenon. Dependent claim 108 also recites the natural phenomenon relating to measuring a particular set of genes, excluding a whole genome. Therefore, claims 98-108 recite a law of nature or natural phenomenon.[Step 2A, Prong 1: YES]
Step 2A: Prong 2: Under the MPEP § 2106.04, the Step 2A, Prong 2 analysis requires identifying whether there are any additional elements recited in the claim beyond the judicial exception(s), and evaluating those additional elements to determine whether they integrate the exception into a practical application of the exception. This judicial exception is not integrated into a practical application for the following reasons.
Dependent claims 100 and 104-105 do not recite any elements in addition to the judicial exception, and thus are part of the judicial exception.
The additional elements of claims 98-99, 101-103, and 106-108 include:
an array (claim 98);
measuring.. (claim 99);
measuring…is performed using a method selected from the group consisting of Southern hybridization, Northern hybridization, polymerase chain reaction (PCR), reverse transcriptase PCR (RT-PCR), quantitative real-time PCR (qRT-PCR), nanoarray, microarray, microarray, autoradiography, and in situ hybridization (claim 101);
wherein measuring the expression…is performed using binding moieties selectively binding to nucleic acid molecules encoding each of the biomarkers (claim 102);
wherein measuring the expression of the nucleic acid molecules is performed using an array (claim 103);
wherein the array comprises different binding moieties, wherein each binding moiety selectively binds to a different nucleic acid molecule, and wherein the array comprises binding moieties selectively binding to nucleic acid molecules (claim 106);
wherein the binding moieties are immobilized on a solid support (claim 107);
wherein the array comprises binding moieties selectively binding to nucleic acid molecules (claim 108);
The additional elements of claim 98 is an array with a solid support for which the binding moieties are immobilized to. The limitation only serves to link the law of nature to a particular technological environment of “arrays”, which does not integrate the law of nature into a practical application. As explained by the Supreme Court, a claim directed to a judicial exception cannot be made eligible "simply by having the applicant acquiesce to limiting the reach of the patent for the formula to a particular technological use." Diamond v. Diehr, 450 U.S. 175, 192 n.14, 209 USPQ 1, 10 n. 14 (1981). Thus simply limiting the naturally occurring binding moieties that specifically bind to biomarkers to the particular technology of an array with a solid support, as opposed to other technologies such as southern hybridization, northern hybridization, or as primers in a PCR reaction does not make the claims eligible.
The additional elements of claims 99, 101-103, and 106-108 similarly merely link the identification of the expressed nucleic acids within dendritic or dendritic like cells to a particular technological environment by requiring the expressed nucleic acids are identified by measuring using one of the recited technologies and/or using binding moieties immobilized on a solid support of an array. Therefore, as discussed above for claim 98, simply limiting the expressed biomarkers to a particular measurement technology such as using binding moieties immobilized on an array, southern hybridization, northern hybridization, or as primers in a PCR reaction does not make the claims eligible. See MPEP 2106.05(h).
Therefore, the additionally recited elements merely link the law of nature or natural phenomenon to a particular technological environment, and thus the claims as a whole do no integrate the abstract idea into practical application. Thus, claims 98-108 are directed to a law of nature or natural phenomenon. [Step 2A, Prong 2: NO]
Step 2B: In the second step it is determined whether the claimed subject matter includes additional elements that amount to significantly more than the judicial exception. See MPEP § 2106.05.
The claims do not include any additional steps appended to the judicial exception that are sufficient to amount to significantly more than the judicial exception for the following reasons.
Dependent claims 100 and 104-105 do not recite any elements in addition to the judicial exception, and thus are part of the judicial exception. The additional elements of claims 98-99, 101-103, and 106-108 are defined above.
The additional elements of an array with binding moieties immobilized on a solid support, as recited in claim 89, and measuring expression levels using binding moieties immobilized on a microarray, as encompassed by claims 99, 101-103, and 106-108, are well-understood, routine, and conventional. This position is supported by Applicant’s own specification in addition to Pascual et al. (A Genomic Approach to Human Autoimmune Disease, Jan. 2010, Annu. Rev. Immunol., 28, pg. 535-571; cited in IDS filed 14 May 2021; previously cited) and Cluzel-Tailhardat et al. (Chemicals with weak skin sensitizing properties can be identified using low-density microarrays on immature dendritic cells, 2007, Toxicology Letters, 174, pg. 98-109; cited on IDS filed 14 May 2021; previously cited).
First, Applicant’s specification at pg. 5, lines 26-28; pg. 10, lines 22-24 and 32-34; pg. 15 lines 28-31 discloses that methods of detecting and/or measuring nucleic acid are well known to those skilled in the art, citing various references and at pg. 6, lines 14-17 discloses microarrays can be used. Applicant’s specification at pg. 20, line 33 to pg. 21, line 17 discloses arrays per se are well known in the art and binding processes for attaching (i.e. immobilizing) binding moieties to the array are well known in the art, citing various reviews providing more information these methods. Furthermore, Pascual et al. (A Genomic Approach to Human Autoimmune Disease, Jan. 2010, Annu. Rev. Immunol., 28, pg. 535-571; cited in IDS filed 14 May 2021), which reviews the use of DNA-based microarrays, which include binding moieties, (Abstract) and discloses the past decade has seen an explosion in the use of DNA-based microarrays (Abstract), and further discloses using microarrays measuring expression levels in treated cells (pg. 536, Col. 2, Par. 1; pg. 544, Col. 1, Par. 1; pg. 459, Col. 1, Par. 1; Figure 9). Last, Cluzel-Tailhardat similarly discloses that various studies in contact allergy have explored gene expression changes in dendritic cells using microarrays (pg. 99, col. 1, para. 2).
Therefore, taken alone, the additional elements do not amount to significantly more than the above-identified judicial exception(s). Even when viewed as a combination, the additional elements fail to transform the exception into a patent-eligible application of that exception. Thus, the claims as a whole do not amount to significantly more than the exception itself. [Step 2B: NO]
Therefore, the instantly rejected claims are not drawn to eligible subject matter as they are directed to a law of nature or natural phenomenon without significantly more. For additional guidance, applicant is directed generally to applicant is directed generally to the MPEP § 2106.
Response to Arguments
Applicant's arguments filed 21 July 2025 regarding 35 U.S.C. 101 have been fully considered but they are not persuasive.
Applicant remarks that claim 98 has been amended to recite that the binding moieties are immobilized on a solid support, and arrays comprising binding moieties immobilized on a solid support are not naturally occurring, and thus claim 98 is patent eligible and is not a product of nature (Applicant’s remarks at pg. 9, para. 2-4).
This argument is not persuasive. While it is agreed arrays comprising binding moieties immobilized on a solid support are not naturally occurring, this is not sufficient to overcome the above rejection. It is important to keep in mind that product of nature exceptions include both naturally occurring products and non-naturally occurring products that lack markedly different characteristics from any naturally occurring counterpart. See, e.g., Ambry Genetics, 774 F.3d at 760, 113 USPQ2d at 1244. See MPEP 2106.04(b). MPEP 2106.04(c) further states if the nature-based product limitation is not naturally occurring, for example due to some human intervention, then the markedly different characteristics analysis must be performed to determine whether the claimed product limitation is a product of nature exception.
As discussed in the above rejection, In Myriad, the Supreme Court made clear that not all changes in characteristics will rise to the level of a marked difference, e.g., the incidental changes resulting from isolation of a gene sequence are not enough to make the isolated gene markedly different. Myriad, 569 U.S. at 580, 106 USPQ2d at 1974-75. See MPEP 2106.04(c). Accordingly, the isolation of such naturally occurring sequences (binding moieties) and immobilization on an array is not sufficient to provide a marked difference in characteristics, given the actual chemical and physical structure and form of the nucleic acids are unchanged. For example, arrays immobilize nucleic acids by placing nucleic acids onto charged substates, which do not require altering the structure or characteristics of the nucleic acid binding moieties relative to their natural counterparts. See Heise et al. (Immobilization of DNA on microarrays, 2006, Top Curr Chem, 261, pg. 1-25; newly cited), which reviews methods of immobilizing DNA on microarrays, including by using non-covalent coupling methods which rely on electrostatic bonds or van der Waals interactions to immobilize the DNA on a charged support (pg. 8, para. 1 through pg. 10; Fig. 8).
Applicant remarks that claim 99 recites a step of measuring expression of nucleic acids in a population of dendritic or dendritic-like cells, and this method step does not recite nor describe any recognized exception, and thus the claim is not directed to an exception under Step 2A (Applicant’s remarks at pg. 9, para. 4 to pg. 10, para. 1). Applicant remarks that claim 99 as a whole indicates an in vitro method for measuring human skin sensitization inducer biomarkers and is not focused on the products per se, and thus there is no need to perform the markedly different characteristics analysis, noting that MPEP 2106.04(c) (I)(C) states “for a process claim, the general rule is that the claim is not subject to the markedly different analysis for nature-based products (Applicant’s remarks at pg. 10, para. 2-3).
This argument is not persuasive. While it is acknowledged that MPEP 2106.05(c) I. C. states that the general rule for a process claim is that the claim is not subject to the markedly different characteristics analysis, MPEP 2106.04(c) goes on to explain in the limited situation where a process claim reciting a nature-based product is drafted in such a way that there is no difference in substance from a product claim, the claim is subject to the markedly different analysis for the recited nature-based product. These types of claims are drafted in a way that focuses on the product rather than the process steps. MPEP 2106.04(c) then provides an example that claims to detecting naturally occurring cell-free fetal DNA (cffDNA) in maternal blood were held to be directed to the cffDNA, because the "existence and location of cffDNA is a natural phenomenon [and thus] identifying its presence was merely claiming the natural phenomena itself." Rapid Litig. Mgmt., 827 F.3d at 1048, 119 USPQ2d at 1374, (explaining the holding in Ariosa Diagnostics, Inc. v. Sequenom, 788 F.3d 1371, 115 USPQ2d 1152 (Fed. Cir. 2015)).
As previously explained, and in explained in the above rejection, the method of claim 99 is similarly focused on the natural phenomenon of the presence of naturally occurring biomarkers in particular natural cell types, and merely links the natural phenomenon to conventional methods for detecting the presence of the biomarkers (i.e. arrays). Thus, similar to the claims in Ariosa Diagnostics, Inc. v. Sequenom, the instant claims only identify the presence of (e.g. measure) a naturally occurring phenomena (the presence of expressed genes within dendritic cells).
Claim Rejections - 35 USC § 102
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 pre-AIA 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) the invention was known or used by others in this country, or patented or described in a printed publication in this or a foreign country, before the invention thereof by the applicant for a patent.
(b) the invention was patented or described in a printed publication in this or a foreign country or in public use or on sale in this country, more than one year prior to the date of application for patent in the United States.
Claims 98-108 are rejected under pre-AIA 35 U.S.C. 102(b) as being anticipated by Lindstedt (2017). Any newly recited portion is necessitated by claim amendment.
Cited reference:
Lindstedt et al., US 2017/0218449 A1 (previously cited).
Regarding claim 98, Lindstedt discloses a microarray for measuring i) squalene epoxidase (SQLE), ii) taste receptor, type 2, member 5 (TAS2R5), iii) keratinocyte growth factor-like protein 1/2/hypothetical protein FLJ20444 (KGFLP1/2/FLJ20444), iv) transmembrane anterior posterior transformation 1 (TAPT1), v) sprouty homolog 2 (SPRY2), vi) fatty acid synthase (FASN), vii) B-cell CLL/lymphoma 7A (BCL7A), viii) solute carrier family 25, member 32 (SLC25A32), ix) ferritin, heavy polypeptide pseudogene 1 (FTHP1), x) ATPase, H+ transporting, lysosomal 50/57 kDa, V1 subunit H (ATP6V1H), and xi) histone cluster 1, H1e (HIST1H1E) (claims 82, 85, and 87). Lindstedt further discloses the microarray includes binding moieties binding moieties, each capable of binding selectively to a nucleic acid molecule encoding one of the biomarkers identified in Table 3 ([0052]), and consists of binding moieties for the 11 markers (i.e. the array is not a complete genome array) ([0131]; [0137]; claim 93, e.g. “consisting of…measuring [the 11 biomarkers]). Lindstedt further discloses the binding moieties are immobilized on a solid support ([0133]).
Regarding claim 99, Lindstedt discloses a method consisting of measuring, in dendritic cells or dendritic like cells exposed to a test agent, the expression of i) squalene epoxidase (SQLE), ii) taste receptor, type 2, member 5 (TAS2R5), iii) keratinocyte growth factor-like protein 1/2/hypothetical protein FLJ20444 (KGFLP1/2/FLJ20444), iv) transmembrane anterior posterior transformation 1 (TAPT1), v) sprouty homolog 2 (SPRY2), vi) fatty acid synthase (FASN), vii) B-cell CLL/lymphoma 7A (BCL7A), viii) solute carrier family 25, member 32 (SLC25A32), ix) ferritin, heavy polypeptide pseudogene 1 (FTHP1), x) ATPase, H+ transporting, lysosomal 50/57 kDa, V1 subunit H (ATP6V1H), and xi) histone cluster 1, H1e (HIST1H1E) (claim 93; [0034]) Given the claim 93 of Lindstedt includes the language “consisting of”, the claim does not measure other biomarkers, such that the method does not comprise measuring a complete genome.
Regarding claim 100, Lindstedt discloses the cells are exposed to a test agent prior to measuring (claims 82, 93).
Regarding claim 101¸ Lindstedt discloses the measuring is performed by a southern blot or microarray ([0029]).
Regarding claim 102, Lindstedt discloses the measuring of expression is performed by binding moieties ([0052]).
Regarding claim 103¸ Lindstedt discloses the measuring is performed by a microarray ([0029]).
Regarding claim 104, Lindstedt discloses the cells can be dendritic like cells (claim 93).
Regarding claim 105, Lindstedt discloses the cells can be MUTZ-3 cells ([0108]).
Regarding claim 106, Lindstedt discloses the measuring is performed by a microarray, wherein the microarray includes binding moieties binding moieties, each capable of binding selectively to a nucleic acid molecule encoding one of the biomarkers identified in Table 3 ([0052]), and consists of binding moieties for the 11 markers (i.e. the array is not a complete genome array) ([0131]; [0137]; claim 93, e.g. “consisting of…measuring [the 11 biomarkers]).
Regarding claim 107, Lindstedt further discloses the binding moieties are immobilized on a solid support ([0133]).
Regarding claim 108, Lindstedt discloses the measuring is by a microarray for measuring i) squalene epoxidase (SQLE), ii) taste receptor, type 2, member 5 (TAS2R5), iii) keratinocyte growth factor-like protein 1/2/hypothetical protein FLJ20444 (KGFLP1/2/FLJ20444), iv) transmembrane anterior posterior transformation 1 (TAPT1), v) sprouty homolog 2 (SPRY2), vi) fatty acid synthase (FASN), vii) B-cell CLL/lymphoma 7A (BCL7A), viii) solute carrier family 25, member 32 (SLC25A32), ix) ferritin, heavy polypeptide pseudogene 1 (FTHP1), x) ATPase, H+ transporting, lysosomal 50/57 kDa, V1 subunit H (ATP6V1H), and xi) histone cluster 1, H1e (HIST1H1E) (claims 82, 85, and 87). Lindstedt further discloses the microarray includes binding moieties binding moieties, each capable of binding selectively to a nucleic acid molecule encoding one of the biomarkers identified in Table 3 ([0052]), and consists of binding moieties for the 11 markers (i.e. the array is not a complete genome array) ([0131]; [0137]; claim 93, e.g. “consisting of…measuring [the 11 biomarkers]). Lindstedt further discloses the binding moieties are immobilized on a solid support ([0133]).
Therefore, Lindstedt anticipates the claimed invention.
Examiner comment:
It is noted this rejection is in light of the 08 March 2021 priority date of set forth above for the instant application, because the priority documents do not provide adequate written description for the broader more generic invention being instantly claimed, for the reasons discussed in the 112 (pre-AIA ), first paragraph rejection above. It is noted the above rejection would be overcome if Applicant amends the claim to consist of measuring the recited biomarkers (and similarly consist of binding moieties for the recited biomarkers), which is supported by the instant application and priority documents (as also applied in the above 102 rejection).
Response to Arguments
Applicant's arguments filed 21 July 2025 regarding 35 U.S.C. 102 have been fully considered but they are not persuasive.
Applicant remarks claims 98-105 are not anticipated by Lindstedt because Applicant has overcome the written description rejection, and therefore, the effective filing date of the claimed invention is 26 Oct. 2010, and Lindstedt is not prior art (Applicant’s remarks at pg. 8, para. 4 to 7).
This argument is not persuasive because the disclosure does not provide adequate written description of the claimed invention as discussed above the priority and under 35 U.S.C. 112 (pre-AIA ) first paragraph sections. Therefore, Lindstedt is prior art and rejection is maintained.
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.
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/KAITLYN L MINCHELLA/Primary Examiner, Art Unit 1685