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 .
Claim Status
Currently, claims 1,5-9,14-15 and 52 are pending in the instant application. Claims 2-4, 10-13, 16-51 have been canceled and claim 52 has been added. As indicated by applicant, claim 16 was withdrawn and should not have been included in the rejections in the previous office action. This action is written in response to applicant' s correspondence submitted 08/05/2025. All the amendments and arguments have been thoroughly reviewed but were found insufficient to place the instantly examined claims in condition for allowance. The following rejections are either newly presented, as necessitated by amendment, or are reiterated from the previous office action. Any rejections not reiterated in this action have been withdrawn as necessitated by applicant' s amendments to the claims. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action. This action is FINAL.
Claims 1,5-9,14-15 and 52 are pending. Claim 1 and 9 are under examination with respect to LTR66 and POU5F1B. Claim 8 and 52 are under examination with respect to SEQ ID NO 5.
Withdrawn Rejections
The objection to claim 8 is withdrawn in view of the amendment to the claims.
The objection to the specification is withdrawn in view of the amendment to the specification.
The rejection of claims 1-16 under 35 USC 112(b) is withdrawn in view of the amendment to the claims.
Maintained Rejections
Improper Markush
Claim 1, 8-9 and 52 are rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
This rejection was previously presented and has been rewritten to address the amendment to the claims including newly added claim 52.
The Markush grouping of transposable elements of LTR66, MIR, MIRb, L2b, L2c, LTR33, and nucleic acid sequence of SEQ ID NO 1-5, is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use.
The members of the improper Markush grouping do not share a substantial feature and/or common use that flows from the substantial structural feature because each member of the transposable elements of LTR66, MIR, MIRb, L2b, L2c, LTR33, and nucleic acid sequence of SEQ ID NO 1-5 are structurally unique relative to one another. There is no disclosed common substantial structural feature and the genes do not share a single structural similarity, as each gene represents a different gene with a different transposable element that has no substantial common nucleotide sequence. The only structurally similarity present is that each gene and transcript comprises nucleic acid molecules. The fact that the genes, transcripts and transposable elements comprise nucleotides per se does not support a conclusion that they have a common single structural similarity because the structure of comprising a nucleotide alone is not essential to the common activity of being correlated to detecting or predicting likihood of cancer. Accordingly while the different genes are asserted to have the property of being indicative of detecting or predicting likihood of cancer, it is not clear from their very nature or from the prior art that all of them possess this property. The nature of different genes is that they are differently expressed in different disorders and result in different transpochimeric gene transcripts. Following this analysis, the claims are rejected as containing an improper Markush grouping.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
Response to Arguments
The response traverses the rejection on pages 7-8 of the remarks mailed 08/05/2025. The response asserts that the group including LTR66, MIR, MIRb, L2b, L2C, LTR33 are transposable elements that are in the first exon of the claimed POU5F1B gene and SEQ ID NO 1-5 include one claimed TE and claimed POU5F1B. The response asserts that the listed alternatives share a common structure feature and common use. This response has been reviewed but not found persuasive. The only common structure that the alternatives comprise a nucleic acid sequence. While each transposon element is fused to POU5F1B, this fusion is not identical in each of the cases and the transposon element is structurally distinct for each recited TE and within each SEQ ID NO. The fact that the cDNA and SEQ ID NOs comprise nucleotides per se does not support a conclusion that they have a common single structural similarity because the structure of comprising a nucleotide alone is not essential to the common activity of being correlated to detecting or predicting likihood of cancer. Accordingly while the different cDNA and SEQ ID Nos are asserted to have the property of being indicative of detecting or predicting likihood of cancer, it is not clear from their very nature or from the prior art that all of them possess this property. Additionally there is not a common structure among the alternatives as such of the TE and POU5F1B comprise different fusion products. For these reasons and reasons of record the rejection is maintained.
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 1,5-9,14-15 and 52 are rejected under 35 U.S.C. 101 because the claimed invention is directed to law of nature/abstract idea without significantly more. The claims recite an abstract idea and are directed to a law of nature. These judicial exception are not integrated into a practical application and the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception for the reasons that follow. This rejection was previously presented and has been rewritten to address the amendment to the claims.
The following inquiries are used to determine whether a claim is drawn to patent-eligible subject matter.
Step 1. Is the claim directed to a process, machine, manufacture, or composition of matter? Yes, all of the claims are directed to a process.
Step 2A. Is the claim directed to a law of nature, a natural phenomenon or an abstract idea (judicially recognized exception) and does the claim recite additional elements that integrate the judicial exception into a practical application?
Yes, the claims are directed to law of nature/natural phenomenon. Claim 1 recites predicting the likelihood of a cancer in a subject by detecting presence or absence of LTR66 and POU5F1B. Claim 9 recites classifying a cancer subject comprising detecting TE and POU5F1B and classifying the cancer subject as favorable based on absence and poor based on presence of POU51B. Claim 6, 7, 14, and 15 require specific cancers. The recited relationship is a natural phenomenon that exists apart from any human action. This type of correlation is a consequence of natural processes.
The claims also recite the judicial exception of an abstract idea and particularly mental processes. Claim 1 recites the abstract idea of a mental process. Claim 1 recites the step of detecting the presence or absence of cDNA comprising LTR66 and POU5F1B. Claim 9 recites the step of “classifying” prognosis based presence or absence of one nucleic acid sequence in the biological sample. Neither the specification or the claims set forth limiting definition for determining or identifying and the claims do not set forth how detecting indirectly or classifying is accomplished. The broadest reasonable interpretation of detecting and classifying step is a step that can be accomplished mentally by evaluating data and critical thinking process wherein one mentally reads information in a database or report regarding the presence or absence of a nucleic acid then draws a mental conclusion. Such “detecting” and “classifying” thereby encompasses process that may be performed mentally and this is an abstract idea.
Having determined that the claims recite a judicial exception, it is then determined whether the claims recite additional elements that integrate the judicial exception into a practical application.
The claims do not recite additional steps or elements that integrate the recited judicial exceptions into a practical application of the exception(s). For example, the claims do not practically apply the judicial exception by including one or more additional elements that the courts have stated integrate the exception into a practical application:
An additional element reflects an improvement in the functioning of a computer, or an improvement to other technology or technical field;
An additional element that applies or uses a judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition;
An additional element implements a judicial exception with, or uses a judicial exception in conjunction with, a particular machine or manufacture that is integral to the claim;
An additional element effects a transformation or reduction of a particular article to a different state or thing; and
An additional element applies or uses the judicial exception in some other meaningful way beyond generally linking the use of the judicial exception to a particular technological
environment, such that the claim as a whole is more than a drafting effort designed to monopolize the exception.
In addition to the judicial exceptions the claims recite specific cancers, specific gene, and RNA transcript that is a transpochimeric gene transcript. These additional steps/elements are not considered to integrate the judicial exception into a practical application because they merely add insignificant extra-solution activity (data gathering) to the judicial exception.
Step 2B - Does the claim recite additional elements that amount to significantly more than the judicial exception? No.
Herein the claims as a whole are not considered to recite any additional steps or elements that amount to significantly more than well-understood, routine, and conventional activities in the art and do not add something “significantly more” so as to render the claims patent-eligible.
The step of detecting the presence or absence of a nucleic acid sequence merely instructs a scientist to use well established, routine and conventional nucleic acid techniques to gather samples for diagnostic analysis. As address in the instant specification methods of detection are well-known (see pg. 11-12).
The step of detecting at least one nucleic acid sequence comprising a transposable element and POU5F1B constitutes a data gathering step required to apply the law of nature/natural phenomenon. It is acknowledged that the claims name particular genes and transposable elements, LTR66 and POU5F1B whose presence is to be detected however the claims do not require a particular, non-conventional primer or probe consisting of or comprising a specific nucleotide sequence or any other specific reagent that is used to accomplish such detecting such that the claims would recite significantly more than the judicial exception. The targets to be detected are part of the judicial exception and thereby the naming of the targets does not add something “significantly more” to the recited judicial exceptions.
The additional steps and elements are recited at a high degree of generality and are all routine, well understood and conventional in the prior art. The recited steps and elements do not provide inventive concept necessary to render the claims patient eligible. There is no combination of elements in this step that distinguishes it from well-understood, routine and conventional data gathering activity engaged in by scientists prior to applicant’s invention and at the time the application was filed. Many cited prior art references in this record demonstrate that these techniques were conventional at the time of the invention. The prior art of Skog (US2014/0045915 A1) teaches is was known in the art to teach fragments and variant of LTR66 and POU5F1B in cancer. Thus the prior art and specification demonstrates it was routine, well-known and conventional in the art to determine POU5F1B and LTR in biological samples. Dependent claims 6-7 and 14-15 further limit the recited judicial exception. Claim 2-5 and 8-13 further describe the gene and transcript detected. The dependent claims do not provide significantly more to the claims outside of the judicial exception as they encompass conventional techniques as described in the instant specification as noted above.
Response to Arguments
The response traverses the rejection on page 8-9 of the remarks mailed 08/05/2025. The response asserts that the claims have been amended to recite a series of steps, extracting, producing and detecting where the producing steps including cDNA from extracted RNA transcripts. The response asserts that this step contributes an inventive concept that amounts to significantly more than the judicial exception of a natural phenomenon. The response asserts that the method integrates the natural starting material into a practical application that satisfies the requirement of step 2 of the Mayo/Alice analysis. This response has been reviewed but not found persuasive. The steps of extracting and producing are data gathering steps that do not integrate the judicial exceptions within the claim. The claims do not require additional elements that apply or use the judicial exception beyond generally linked the use of the judicial exception to a particular technological environment. Additionally the step of producing is not an inventive concept because it was routine and conventional in the art to produce cDNA from extracted RNA transcripts. This step encompasses using well established, routine and conventional nucleic acid techniques to gather samples, extract RNA and detect cDNA by producing cDNA from extracted RNA. The claims do not require a particular non-conventional primer or probe or other specific reagent that is used to accomplish producing or detecting such that the claims would recite significantly more than the judicial exception. The targets to be detected are part of the judicial exception and there is no additional steps that are not conventional in the prior art. The additional steps of extracting, producing and detecting are all routine, well understood and conventional in the prior art and do not provide inventive concepts necessary to render the claims patent eligible. There is no combination of elements in these steps that distinguish it from well-understood, routine and conventional data gathering. For these reasons and reasons of record this rejection is maintained.
Claim Rejections - 35 USC § 112-Description
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 1,5-9,14-15 and 52 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 was previously presented and has been rewritten to address the amendment to the claims.
The claims are drawn to methods for detecting, predicting and classifying a cancer in a subject comprising detecting directly or indirectly by presence or absence of at least one nucleic acid sequence comprising at least one transposable element, a fragment or variant thereof and at least one gene sequence, a fragment or variant thereof. The elected gene and transposon is POUF51B and LTR66. RNA transcript is transpochimeric gene transcript (claim 5). Claims further encompass cancer is colorectal cancer (claim 7 and 15).
The claims do not define the variant or fragment in terms of any structural such as type of mutation type (insertion, deletion, substitution, translocation) the number of nucleotides encompassed by the mutation or fragment, the identity of the nucleotides (A, G, T or C) of the variant or the size of the fragment. Accordingly the claimed genus of one transposable element, LTR66 fragment or variant and POU5F1B, fragment or variant sharing 80% sequence homology consistent with the election is considered to be significantly large given the fact that the claims encompass any single or multiple nucleotide insertion, deletion or addition at any position within the large genus of transposable elements and even within the gene POU5F1B sequence
The specification discloses 5 chimeric gene transcripts that include a fragment of POU5F1B (see table 1) that was identified in a group of patients with colorectal cancer (see table 1). The specification discloses only colorectal cancer in humans with POU5F1B and LTR66, LTR33, L2B, and L2c and specific sequences of SEQ ID NO 1-5. . The specification does not teach any other cancers with SEQ ID NO 1-5 and does not teach any other subjects other than humans.
Thereby, while the specification has adequately described SEQ ID NO 5, consistent with the elected species and association with colorectal cancer in human subject, the specification has not adequately described a representative number of fragments or variants of the large genus of transposable element, or even a representative number of fragments or variants of LTR66 and fragments and variants of POU5F1B that are 80% homologous in a representative number of cancers. Additionally the specification has not provided a representative number of TcGT and association with the broad genus of cancers.
No additional members of the claimed genus of transposable elements, fragments and variants and POU5F1B, fragments and variants that are 80% homologous and cancers have been sufficiently described in terms of any other relevant identifying characteristics. Relevant to the lack of particular structural limitations in the rejected claims, MPEP 2163 states:
The claimed invention as a whole may not be adequately described if the claims require an essential or critical feature which is not adequately described in the specification and which is not conventional in the art or known to one of ordinary skill in the art.
Additionally, the specification does not disclose a clear structure-function relationship between the claimed TcGTs and additional cancers. There is no showing or evidence which links particular TcGT, fragments or variants of POU5F1B, fragments or variants of LTR66 and cancer. In the absence of any real structure-function relationship in a representative number of fragments, variants of LTR66 that is 80% homologous and fragments and variants 80% homologous of POU5F1B and in the absence of a representative number of cancer, there is insufficient descriptive support for the currently claimed genus of any fragment or variant of POU5F1B, any broad genus of any fragment or variant of LE, broad genus of any cancer, and any subject. While limitations from the specification are not read into a claim, a claim must be read in view of the specification.
It is acknowledged that the specification also teaches the general methodology for detecting a variant, fragment or TcGT. However, possession may not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features. Thereby, a showing of how to potentially identify TcGTs, fragments and variants of LE and POU5F1B is not sufficient to establish that Applicants were in possession of the invention as broadly claimed.
With respect to the present invention, there is no record or description which would demonstrate conception of a representative number of fragments, variants 80% homologous or TcGT, specifically the elected LTR and POU5F1B that are linked to any cancer. The specification does not disclose a representative number of fragments and variants of TE and POU5F1B or LTRs and POU5F1B that are associated in any subject in a representative number of cancers. Therefore, the claims fail to meet the written description requirement because the claims encompass a significantly large genus of variants of TE and POU5F1B and large genus of TcGTs which are not described in the specification that would be associated with the large genus of cancers.
Response to Arguments
The response traverses the rejection on page 9-10 of the remarks mailed 08/05/2025. The response asserts that POU5F1B gene has been linked to gastric, prostate, liver, and breast cancer and applicant detected POU5F1B-related transpochimeric transcripts not only in CRC but also metastatic tissue of other primary tumors and points to fig 10 of the specification and fig 6 of Simu-Riudalbas (2022). The response asserts that the data demonstrate that tumor-preferential overexpression of POU5F1B through oncogenic exaptation of normally silenced TE promoters is widespread in human cancers. The response asserts that the ordinary artisan would be ablet o make and use the claimed invention despite any reasonable and customary experimentation that may be required.
This response has been thoroughly reviewed but not found persuasive. The claims are not limited to detecting overexpression of POU5F1B. Figure 10 of the specification shows expression of POU5F1B. Figure 10 demonstrates that none of the primary tumors present POU5F1B transpochimeric transcripts (see pg. 5). Therefore figure 10 does not provide support for the genus of LTR66 fused POU5F1B presence and variants thereof with a representative number of solid cancers. The claims require detecting the presence or absence of LTR66 fused to POU51B and variants thereof with 80% sequence homology and classifying the solid cancer subject as favorable or good prognosis. The specification does not disclose any variant of LTR66 fused to POU51B. Figure 10 demonstrates metastases and expression of POU51B. Figure 10 does not describe transpochimeric transcripts of POU5F1B with a representative number of solid tumors nor does Figure 10 provide a representative number of variants of LTR66 fused to POU51B with a representative number of cancers. Neither the specification or the prior art demonstrate a representative number of LTR fused POU51B or variants thereof that are associated with a representative number of solid cancers. The specification describes LTR66 fused to POU51B, SEQ ID NO 5 is associated with colon cancer but there are no other species disclosed within the genus claimed. For these reasons and reasons of record the rejection is maintained.
Claim Rejections - 35 USC § 112-Scope of Enablement
Claims 1,5-9,14-15 and 52 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method for predicting likihood of colorectal cancer in a human subject, the method comprising obtaining a sample from the subject and detecting the presence of SEQ ID NO 5 in the sample, does not reasonably provide enablement for the claims as written. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims. This rejection was previously presented and has been rewritten to address the amendment to the claims.
Factors to be considered in determining whether a disclosure meets the enablement requirement of 35 USC 112, first paragraph, have been described by the court in In re Wands, 8 USPQ2d 1400 (CA FC 1988). Wands states at page 1404,
“Factors to be considered in determining whether a disclosure would require undue experimentation have been summarized by the board in Ex parte Forman. They include (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims.”
Nature of the invention and breadth of the claims
The claimed methods are drawn to detecting, predicting likihood, and classifying cancer in a subject detecting y in a biological sample the presence or absence of cDNA comprising LTR66 fused to POU5F1B, fragment or variants that are 80% homologous. Dependent claims encompass detecting RNA transcript that is a transpochimeric gene transcript (TcGT), TcGT a nucleic acid that is SEQ ID NO 5, colorectal cancer.
The claims generically encompass the analysis and detection of any cDNA comprising LTR66 fused to POU5F1B, fragment or variants that are 80% homologous. The claims encompass the association of any of nucleic acids with any cancer.
The claims thus require knowledge of reliable and robust association between the presence of any cDNA comprising LTR66 fused to POU5F1B, fragment or variants that are 80% homologous with any cancer in a human subject.
Direction provided by the specification and working example
The instant specification provides an example wherein datasets from human subjects were aligned to hg19 genome assembly. The datasets analyzed were data from CRC patients and normal patients. The data analysis identified transpochimeric transcripts and identified SEQ ID NO 5 (LTR66-POU5F1B) that was expressed in 0 out of 18 normal samples, 10 out of 18 primary CRC samples and 14 out of 18 liver metastases. Analysis of a second set indicated survival rates however there was statistical analysis of the association of the identified TcGT with survival or prognosis or identification of a TcGT present (see table 1). Relevant to the methods of the pending claims, the data of the specification (e.g.: example 1 and table 1) indicate that SEQ ID NO 5 was found to be susceptible to colorectal cancer in human subjects.
There is no analysis that the presence of any variant or fragment of TE and POU5F1B is associated with cancers. There is no analysis that SEQ ID NO5 is found in any other cancers. The specification does not teach any other TcGTs of POU5F1B and any TE other than SEQ ID NO 5 is associated with any cancer, including colorectal cancer. The specification teaches only that SEQ ID NO 5 is associated with colorectal cancer in human subject but there is no data or analysis that any other variant or fragment of POU5F1B with any fragment or variant TE or LTR would be associated with cancer prediction.
State of the art, level of skill in the art, and level of unpredictability
While the state of the art and level of skill in the art with regard to identification of known TE and gene fragment, variant, or TcGT in human samples is high, the unpredictability in associating any particular alteration with a specific phenotype, or identifying a particular TcGT in a heterologous organism, as is encompassed by the claims, is even higher. The unpredictability is demonstrated by the related art and the instant specification.
Because TcGT were found by analysis of RNA-Seq data, the art teaches the challenges of analyzing biomarker identification using RNA-Seq data. Tong (Scientific Reports, 2020, 110:17925, pp 1- teaches using cross validate using three classifiers when using RNA-seq data for disease outcome prediction and AUC and MCC (see pg. 4). Here the specification does not provide any cross validation or use three classifiers for disease outcome prediction of the elected SEQ ID NO 5 with colorectal cancer much less the genus encompassed by the claims.
Grundy (FEBS Journal, 2022, 289, pp1160-1179) teaches reviews the role of TEs and cancer. Grundy teaches regulation of TEs is fairly well characterized. Grundy teaches further investigation is required in order to determine the feasibility of utilizing TEs as potential cancer biomarkers for specific cancers (see pg. 1171, last para). Grundy teaches that while TEs are understood their association with cancer requires further investigation, thus demonstrates that detecting any TE, transcript or fragment with POU5F1B would be unpredictable to associate with any cancer.
Applicants own work demonstrates that it is unpredictable to identify SEQ ID NO 5 with other cancers. Simo-Riudalbas et al (Nature Communications, 2022, 13:4913, 1-17) teaches that TLR66-POU5F1B transcript was predominate in CRC shorter versions were more frequent in other cancers (see figure 6a) (p. 6, 2nd column, last para). Simo-Riudalbas demonstrates that SEQ ID NO 5 is not associated in other cancers and that shorter versions of the TcGT are associated, demonstrating that it is not predictable to determine which TcGT will be associated with a specific cancer.
Quantity of experimentation required
A large and prohibitive amount of experimentation would be required to make and use the claimed invention. Given that the claims generically encompass any subject, any cancer, any transposon element, fragment or variant and any fragment or variant of POU5F1B one would have to perform large case: control studies, and validation of any results, to determine which TE and which fragment or variant of POU5F1B in any subject occur and may be reliably and robustly associated with any type of cancer. Even for the particular elected SEQ ID NO 5, given the lack of consistent statistically significant results with regard to classifying and predicting prognosis of any cancer, one would have to perform an analysis to see if even the elected TcGT is robustly and reliably associated with any cancer, colorectal cancer in any subject or prognosing and classifying colorectal cancer.
Conclusion
Taking into consideration the factors outlined above, including the nature of the invention and breadth of the claims, the state of the art, the level of skill in the art and its high level of unpredictability, and the particular guidance in the specification including the examples, it is the conclusion that an undue amount of experimentation would be required to make and use the invention as claimed.
Response to Arguments
The response traverses the rejection on page 10-11 of the remarks mailed 08/05/2025. The response asserts there is no undue experimentation for an ordinary skilled artisan to make and use the entire scope of the claimed invention and Applicant has provided sufficient guidance to enable one of skill in the art to make and use the invention. The response asserts the claims have been amended to encompass solid cancer in a human subject and variant is limited to sharing more than 80% sequence homology. This response has been thoroughly reviewed but not found persuasive. The response asserts the specification provides sufficient guidance but provides no evidence of the sufficient guidance. As addressed in the rejection, there is no data or analysis that any other variant of POU5F1B other than SEQ ID NO 5 that is associated with colorectal cancer. The specification provides a working example and guidance of the association of SEQ ID NO 5 with colorectal cancer but provides no guidance for the genus of LTR fused to POU5F1B and variants thereof with solid cancers. Figure 10 demonstrates that none of the primary tumors present POU5F1B transpochimeric transcripts. Additionally the cited art demonstrates the unpredictability of using RNA-seq data for biomarker identification, TEs as potential cancer biomarkers for specific cancers requires further investigation, and SEQ ID NO 5 is not associated in other cancers except CRC. Therefore given the lack of guidance in the instant specification coupled with the prior art, it would require undue experimentation to make and use the invention as claimed. For these reasons and reasons of record, the rejection is maintained.
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 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.
Claims 1, 5-9,14-15 and 52 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Skog (US2014/0045915 A1). This rejection was previously presented and has been rewritten to address the amendment to the claims.
With regard to claim 1-3, 5, 9-13 Skog teaches analysis of biological materials for biomarkers associated with diagnosis, prognosis, and risk assessment of disease (see para 12). Skog teaches biomarkers include genetic aberrations (see para 13). Skog teaches the genetic aberration includes a transposable element or fragment thereof (see para 14) and can include a cancer gene (see para 17) (claim 3-4 and 12). Skog teaches the disease may be brain cancer (See para 20). Skog teaches detecting POU5F1B in cancer (See para 57, para 312) (claim 2 and 10-11).
With regard to claim 4, Skog further teaches detecting TEs in cancer, include LTR66 (see table 4).
It is noted that the claims recite detecting the presence or absence of at least one nucleic acid sequence comprising at least LTR66 fused to POU5F1B or variants or fragments 80% identical. The claims encompass teaches detecting the absence of LTR66 fused to POU5F1B. Skog does not teach detecting the cDNA comprising the fusion and therefore encompass teaching the absence of LTR66 fused to POU5F1B
Additionally with respect to claim 5 and claim 13, the claims require a RNA transcript is transpochimeric gene transcript but the claims include detecting the absence. Skog does not detect a POU5F1B TcGT and therefore meets the limitations of the claims as the claims encompass detecting the absence.
With regard to claim 6-7 and 14-15, Skog teaches cancer encompasses colon (see para 102). Response to Arguments
The response traverses the rejection on page 11-12 of the remarks mailed 08/05/2025. The response asserts the claim amended require the TE and POU5F1B to be fused. The response asserts that Skog does not disclose a genetic aberration being an RNA transcript comprising at least one TE and a POU5F1B. This response has been thoroughly reviewed but not found persuasive. The claims recite detecting the presence or absence of at least one cDNA of the extracted RNA transcripts comprising a TE fused to POU5F1B. Because Skog does not teach detecting a TE fused to POU5F1B, Skog teaches detecting the absence of TE fused to POU5F1B and therefore anticipates the claimed invention. For these reasons and reasons of record the rejection is maintained.
Conclusion
No claims are allowable.
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 SARAE L BAUSCH whose telephone number is (571)272-2912. The examiner can normally be reached M-F 9a-4p.
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/SARAE L BAUSCH/Primary Examiner, Art Unit 1699
