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, 3, 5, 7-8, 13, 20, 23-32, 58-61 are pending in the instant application. Claims 2, 4, 6, 9-12, 14-29, 21-22, 33-57 have been canceled and claims 58-61 have been added. This action is written in response to applicant’s correspondence submitted 11/26/2025. 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 Any rejections not reiterated in this action have been withdrawn as necessitated by applicant’s amendments to the claims.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, 3, 5, 8, 20, 23-32, 58-61 are under examination. Claim 8 is under examination with respect to 8 genes comprising BRCA1, BRCA2, PMS2, RAD51, RAD54L, RAD54B, FANCL, and POLG.
Maintained Rejections
Improper Markush Rejection
Claim 8 is 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.
The Markush grouping of ATM, BRCA2, CHEK2. ERCC2, FAN], FANCA, FANCC, FANCD2, FANCI, FANCL, GTF2H5, MLH3, MSH2, MSH6. MUTYH, NBN, OGG 1, POLG, POLH, and RAD51C is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons:
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 genes recited in claim 8 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 that has no substantial common nucleotide sequence. The only structurally similarity present is that each gene comprises nucleic acid molecules. The fact that the genes 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 classifying a sample. Accordingly while the different genes are asserted to have the property of having a pathogenic mutation and indicative or prostate 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. 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 page 6-7 of the remarks mailed 11/26/2025. The response asserts that PTAB reviewed a Markush rejection in Ex parte Narva, asserting that a single structural similarity does not require nucleotide sequence level granularity and that the sequences of the Markush group were not improper. The response address that the PTAB observed that the nucleic acid sequences belong to the same recognized chemical call of polyribonucleotide’s with the common use of silencing ROP proteins. The response asserts that Ex Parte Narva finds that claims reciting alternative molecules compose of different biological sequences may satisfy the requirement of proper Markush group. The response asserts that the different biological sequences gelong to the same recognized chemical and scientific class of DDRG that encode proteins and the presence of a mutation can increase a patient’s risk for developing prostate cancer. The response asserts that mutations in the genes of claim 8 may be commonly used to identify subjects having predisposition for developing prostate cancer. The response asserts that the recited genes belong to the single recognized scientific class of DDR genes and share the same diagnostic use, detecting DDR associated with prostate cancer risk, the group is a proper Markush grouping. This responses has been thoroughly reviewed but not found persuasive.
With regard to Ex Parte Narva, the claims were directed to ROP nucleic acids wherein the nucleic acids were from different insects or comprised different position of the ROP sequence and the ROP nucleic acids all shared the common function of silencing the same ROP proteins. PTAB concluded that the ROP nucleic acids did share a single similarity and common use. In contrast the genes are not from different species nor do the genes comprise fragments of the same sequence, the claims are not directed to the same gene from different species or the fragments of the same gene. Rather, the recited genes each have distinct nucleotide sequences and they do not share a single significant structural similarity. The claims require that mutations within the genes are associated with prostate cancer however there is not a single common mutation within the genes are associated with prostate cancer. The claim requires a pathogenic gene mutation but there is not a common structure that is required for a pathogenic gene mutation. Because the nucleic acid sequences do not share a common structure and a common function, the sequences do not comprise a proper Markush grouping. 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, 3, 5, 8, 20, 23-32, 59-61 are rejected under 35 U.S.C. 101 because the claimed invention is directed to judicial exception without significantly more. The claims recites an abstract idea and a law of nature. This judicial exception is 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. 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 identifying and managing a subject having a predisposition for developing prostate cancer. Claim 3 recites subject identified as having the prostate cancer predisposition for development of prostate cancer. Claim 55 recites a subject suspected of having ga predisposition for developing prostate cancer. Each of the claims require one pathogenic or likely pathogenic mutation in BRCA1, PMS2, RAD51, RAD54B, and RAD54L. 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, 3, 20, 25, 29, 51, 58-61 recites the abstract idea of a mental process. Claim 1 recites the step of “determining” if the biological sample contains at least one pathogenic or likely pathogenic mutation, “identifying” as having a predisposition for developing prostate cancer and “monitoring” the subject. Claim 3 recites a “subject identified as having prostate cancer predisposition” and “determining” if the biological sample contains at least one pathogenic or likely pathogenic mutation, and selectin ga treatment. Claim 20 recites “before determining” if the biological sample contains at least one pathogenic or likely pathogenic mutation in the plurality of genes. Claim 25 recites providing genetic counseling to the patient.. Neither the specification or the claims set forth limiting definition for determining, identifying, or selecting and the claims do not set forth how determining, identifying or selecting is accomplished. The broadest reasonable interpretation of the determining, selecting, and identifying 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 mutations then draws a mental conclusion. Such “determining” “Selecting” and “identifying” 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.
It is noted that the claims recite a step of “treating a subject identified as having” and “further comprising a step of treating” the subject identified (claim 29). Claim 4 and 30-32 recite specific therapies. Claim 3 requires treating only if a subject is identified as having predisposition to prostate cancer without identifying a subject as having prostate cancer. Claim 3 preamble recites a method of treating a subject with prostate cancer however none of the treating steps treat a subject with prostate cancer the only treatment step that occurs is for a subject identified as having prostate cancer predisposition which is not related to the assaying and determining step as these steps require the subject has prostate cancer. Claim 28 encompasses any therapy and only occurs if a mutation is detected. Claim 28 does not require any specific mutation other than a pathogenic or likely pathogenic mutation. Additionally dependent claims 31-32 while reciting specific therapies do not integrate the judicial exception because the step of treating is conditional and is not specific to any specific patient population.
As mentioned above, a claim limitation can integrate a judicial exception by applying or using the judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition. When evaluating this consideration one must the following:
(i) the particularity or generality of the treatment or prophylaxis limitation;
(ii) whether the limitations have more than a nominal or insignificant relationship to the exception; and
(iii) whether the limitations are merely extra solution activity or field of use.
The steps of “treating” a subject identified as having predisposition to prostate cancer (claim 3, 5) and treating the subject if a pathogenic or likely pathogenic mutation is identified (claims 29-32) are not particular i.e., specifically identified so that it does not encompass all applications of the judicial exception. In other words the claims broadly encompass a mental step of identifying a subject and treating. With regard to claim 29-32, the step of treating is conditional and is not specific. The step only occurs if a subject is identified and it encompasses any and all treatment. Additionally the treatment limitations do not appear to have a significant relationship to the exception. Treating a subject only occurs if a pathogenic or likely pathogenic mutation is identified in any of the recited genes (claims 29-32). The recited steps are conditional in claims 29-32. Claim 25 recites providing genetic counseling, however genetic counseling is considered a mental process that encompasses advising or informing without any physical administrative steps. For these reasons the selecting, treating, and counseling steps does not integrate the judicial exceptions into a practical application.
In addition to the judicial exceptions the claims recite specific genes (claim 8), blood sample (claim 24), patient population (claim 23, 52-54) and assaying conditions (claim 19-20). (claim 2-3). 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 obtaining a biological sample and assaying a DDR gene for a pathogenic mutation merely instructs a scientist to use well established, routine and conventional nucleic acid techniques to gather samples for diagnostic analysis. As address below methods of assaying for pathogenic mutations are well-known in the art (See para 73).
The step of assaying a sample to determine pathogenic or likely pathogenic mutations in the elected genes, constitutes a data gathering step required to apply the law of nature/natural phenomenon. It is acknowledged that the claims name particular genes whose mutation is to be determined 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 determining 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 Matsugushi (US2018/0089373 A1) demonstrates assaying biological sample by sequence analysis to determine mutations in BRCA1, BRCA2, FANCL, PMS2, POLG, RAD51, RAD54B, RAD54L and selecting therapy. Castro (J Clin Oncol 2019 37:490-503) teaches assaying biological samples for pathogenic mutations in BRCA1, BRCA2, FANCL, PMS2, POLG, RAD51, RAD54B, RAD54L in prostate cancer and selecting therapy. Thus the prior art and specification demonstrates it was routine, well-known and conventional in the art to determine pathogenic mutations in BRCA1, BRCA2, FANCL, PMS2, POLG, RAD51, RAD54B, RAD54L in biological samples including blood samples and in patients with prostate cancer and of African descent. 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 11/26/2025. The response points to example 29 of the USPTO Subject Matter Eligibility Example. The response asserts that claim 1 and claim 51 describe analogous management steps and these claims recite a step of monitoring the subject identified as having prostate cancer predisposition for development of prostate cancer wherein the monitoring comprises PSA testing. The response asserts that the monitoring step which utilizes PSA testing is a specific and concrete action that integrates the alleged judicial exception into a practical application. This response has been reviewed but not found persuasive. The recitation of monitoring comprises PSA testing does not require performing PSA testing on the subject. Claim 1 is not analogous with example 29 of the written guidelines, example 29 recites administering a specific therapy to the diagnosed patient and requires diagnosing a subject, in claim 1 there is no specific therapy that is being administered to the subject, the claim recites a step of monitoring, monitoring does not encompass administering therapy. The broadest reasonable interpretation of this step encompasses reading results of PSA test or indicating to the subject to include PSA testing without performing PSA testing on the subject. For example the medical professional could read the results of PSA testing on a report which would encompass monitoring by PSA testing for the subject. Adding a step that includes a judicial exception does not integrate the natural law or abstract idea of the previous steps recited within the claim.
The response further asserts that claim 3 recites a treatment step. The response asserts that claim 3 does not merely recite a correlation between a gene mutation and disease or encompass only mental steps but applies genetic information within a defined therapeutic protocol and includes concrete treatment steps. This response has been thoroughly reviewed but not found persuasive. Claim 3 requires only treating the subject identified as having prostate cancer predisposition for development of prostate cancer. Claim 3 does not identify a subject having prostate cancer predisposition. Claim 3 recites a method of treating as subject with prostate cancer, assaying a sample from the subject (the subject with prostate cancer) and determining if the sample contains a mutation in the recited genes. The treatment step is not correlated to the assaying or determining step as treating is performed on a subject identified as predisposition for development of prostate cancer, which does not occur in any of the preceding steps. As such the treatment step is not integrated to the determination of mutation status as the step of treating does not recite nor require assaying or determining mutations in the claimed genes.
The response addresses the example 29 of the written guidelines and asserts that the instant claims are analogous to the claim and there is no basis to explain why a treatment step is patent eligible in USPTO guidance but not acceptable in the instant claims. This response has been reviewed but not found persuasive. As addressed above claim 1 and claim 3 are not analogous to example 29. Example 29 recites administering and effective amount of antibodies to the diagnosed patient. In claim 1, there is no treatment step to the identified subject, the step of monitoring is a judicial exception and encompasses a mental step. In claim 3 the step of treating is not correlated to the step of determining mutation. In claim 3, treating occurs when a subject is identified as having a predisposition however it does not recite or require the step of determining a mutation and is not related to the abstract idea recited within the claims. The claims are not analogous to example 29 of the USPTO guidance. 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 3, 5, and 58 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Matsugushi (US2018/0089373 A1). This rejection was previously presented and has been rewritten to address the amendment to the claims.
With regard to claim 58, Matsugushi teaching obtaining a biological sample, assaying biological samples, analyzing samples, and selecting clinical trials (see fig 1) (selecting a treatment). Matsugushi teaches processing the biological data from the subject against a filtered set of therapies to generate the subset of therapies for which the subject qualifies (selecting a treatment) (see para 4 and 10). Matsugushi teaches assaying samples and generating biological data that includes nucleic acid mutations selected from genes and variants of Table 1 (see para 23). Matsugushi teaches identifying genomic aberrations (See para 131) (identifying one pathogenic or likely pathogenic mutation). Matsugushi teaches the subject may be diagnosed with prostate cancer (see para 83). Matsugushi teaches a sample can comprise DNA carrying germline, somatic, or cancer associated mutations (see para 88). Matsugushi teaches the genes and biomarkers include BRCA1, BRCA2, FANCL, PMS2, POLG, RAD51, RAD54B, RAD54L (see para 169).
With regard to claim 3, Matsugushi teaches providing a subject with cancer with a therapy. Matsugushi teaches a method for qualifying a subject for a subset of therapies. Matsugushi teaches biological data is reviewed and the data is used to determine a list of therapies according to a molecule profile of the subject which can be one or more genomic aberrations in the sample. Matsugushi teaches matching targeted therapy to molecular profile (see para 174 and 177). Matsugushi teaches assaying a biological sample for an aberration in BRCA1, BRCA2, FANCL, PMS2, POLG, RAD51, RAD54B, RAD54L (see para 169). Matsugushi teaches recommendation, selection and treatment of therapy that includes chemotherapies, targeted therapies, immunotherapies, and radiotherapies (See para 184) (claim 5).
Response to Arguments
The response traverses the rejection on page 10 of the remarks mailed 11/26/2025. The response asserts claim 3 has been amended to incorporate the features of claim 4 which was not rejected by Matsugushi. This response has been reviewed but not found persuasive. While claim 4 was not previously rejected the amendment to claim 3 not only incorporates some of the limitations of claim 4 but the amendment also renders the claim indefinite for the reasons addressed in this action. Because claim 3 is indefinite and it is not clear who is being treated and how determining mutations is related to the treatment step, Matsugushi has been applied because Matsugushi teaches each of the active process steps within claim 3, as addressed above. Additionally the claims are not limited to only the claimed genes and encompass assaying additional genes as such the teaching of Matsugushi anticipates the claims. For these reasons and reasons of record the rejection is maintained.
Claims 1, 3, 5, 19-20, 26-32, and 58 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Castro (J Clin Oncol 2019 37:490-503). This rejection as previously presented and has been rewritten to address the amendment to the claims.
With regard to claim 1 and 58, Castro teaches assaying a sample and identifying germline DDR mutations (see study design and patients). Castro teaches monitoring PSA levels (see study design and patients and study procedures). Castro teaches assaying in a sample to determine germline mutations in BRCA1, PMS2, RAD51, RAD54B. and RAD54L. Castro teaches identifying pathogenic mutations in BRCA1 and RAD54L (See fig 2B). Therefore Castro teaches assaying a biological sample to determine if the sample has a pathogenetic mutation in BRCA1, PMS2, RAD51, RAD54B and RAD54L and a patient is identified with prostate cancer.
With regard to claim 3-5 and 29-32, Castro teaches assaying a sample and identifying a pathogenic mutations in BRCA1, PMS2, RAD51, RAD54B. and RAD54L (see fig 2B). Castro teaches identifying at least one pathogenic mutation in BRCA1, RAD54L, and PMS2 (see figure 2B). Castro teaches selecting therapy and treating patients including hormone therapy, platinum therapy and PARPi (see table 1)
With regard to claim 19-20, Castro teaches obtaining a sample and sequencing before determining if the sample contains a pathogenic gene mutation (See germline variant analyses).
With regard to claim 26-28, Castro teaches at study entry, patients reported family history of cancer that was significantly more common in gDDR carriers. Castro teaches family history of BRCA2 mutations, breast and ovarian cancer (see germline DNA repair gene mutations and familial cancer history).
Response to Arguments
The response traverses the rejection on page 11 of the remarks mailed 11/26/2025. The response asserts that Castro fails to disclose all the features of claim 1 and claim 3. The response asserts that Castro fails to disclose assaying each of BRCA1, PMS2, RAD51, RAD54B, and RAD54L. The response asserts that Castro identifies 107 genes which may include BRCA1, PMS2, RAD51, RAD54B and RAD54L but the particular subset of genes is not described in Castro. This response has been thoroughly reviewed but not found persuasive. The claims are not limited to assaying only BRCA1, PMS2, RAD51, RAD54B, and RAD54L. The claims recite comprising assaying for each of BRCA1, PMS2, RAD51, RAD54B, and RAD54L, which is anticipated by Castro. Figure 2A of Castro discloses the genes that were assayed for mutations and teaches each of BRCA1, PMS2, RAD51, RAD54B, and RAD54L. Figure 2B of Castro identifies mutations in BRCA1, RAD54L. The claims do not require identifying mutations in each of the genes or require only assaying the BRCA1, PMS2, RAD51, RAD54B, and RAD54L. The claims recite assaying each of the plurality of genes of BRCA1, PMS2, RAD51, RAD54B, and RAD54L, which is disclosed by Castro. For these reasons and reasons of record, the rejection is maintained.
Claims 1, 3-5, 25-32, and 58 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Nombela (Cancers, 2019, vol 11, 352, pp 1-15).
With regard to claim 1 and 58, Nombela teaches assaying a sample and identifying germline DDR mutations (see study design and patients). Nombelo teaches DDR gene screened for mutation in prostate cancer studies by assaying a prostate cancer sample to determine germline mutations in BRCA1, PMS2, RAD51, RAD54B. and RAD54L (see table 1). Nombela teaches monitoring PSA levels in BRCA2 carriers (see pg. 6). Therefore Nombela teaches assaying a biological sample to determine if the sample has a pathogenetic mutation in BRCA1, PMS2, RAD51, RAD54B and RAD54L and a patient is identified with prostate cancer and monitoring PSA levels.
With regard to claim 3, 5 and 29-32, Nombela teaches assaying a sample and identifying a pathogenic mutations in BRCA1, PMS2, RAD51, RAD54B. and RAD54L (see table 1). Nombela teaches identifying at least one pathogenic mutation in BRCA1 and teaches selecting therapy and treating patients which includes surgery and radiotherapy (see 3.1) Nombela further teaches mutations in BRCA and selecting platinum based and PARPi in prostate cancer (see 3.4).
With regard to claim 25-28, Nombela teaches identification of germline mutations in prostate cancer should be followed by genetic testing of all related family members (See pg. 10, last paragraph). Nombela teaches patients eligible for testing may undergo counseling by a urologist or oncologist (See pg. 11, 1st paragraph). Nombela teaches patients with BRCA mutations have other relatives also diagnosed with cancer, including breast cancer (see pg. 10, last paragraph)
Response to Arguments
The response traverses the rejection on page 11-12 of the remarks mailed 11/26/2025. The response asserts that Nombela identifies 107 genes which may include BRCA1, PMS2, RAD51, RAD54B, and RAD54L but the particular subset of genes recites in the claims is not described in Nombela. The response asserts that any anticipation theory would require selecting individuals genes from among 107 DDR genes discussed by Nombela and rearranging them to form Applicant’s specific panel. This response has been reviewed but not found persuasive. The claims do not recite a panel consisting of only BRCA1, PMS2, RAD51, RAD54B, and RAD54L genes, the claims recite a method comprising assaying each of a plurality of genes, wherein the plurality of genes comprise BRCA1, PMS2, RAD51, RAD54B, and RAD54L. The recitation of “comprising” and “comprises” is not closed language but open language and allows for additional genes to be included, including the 107 DDR genes disclosed by Nombela. Nombela teaches assaying for BRCA1, PMS2, RAD51, RAD54B, and RAD54L in additional to other genes however the claims are not limited to assaying only BRCA1, PMS2, RAD51, RAD54B, and RAD54L and therefore Nombela anticipates the claims.
Claim Rejections - 35 USC § 103
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim 23 is rejected under 35 U.S.C. 103 as being unpatentable over Castro (J Clin Oncol 37:490-503) in view of Moses (J. Clinical Oncology, 2018, vol 36, no 6, pp 1-2)
Castro teaches assaying a sample and identifying germline DDR mutations (see study design and patients). Castro teaches assaying in a sample to determine germline mutations in BRCA1, PMS2, RAD51, RAD54B. and RAD54L. Castro teaches identifying pathogenic mutations in BRCA1 and RAD54L (See fig 2B). Therefore Castro teaches assaying a biological sample to determine if the sample has a pathogenetic mutation in BRCA1, PMS2, RAD51, RAD54B and RAD54L and a patient is identified with prostate cancer. Castro does not teach the patient is of African descent.
However Moses teaches prostate cancer patients with metastases or strong family history of cancer are at higher risk of germline mutations in DDR genes. Moses teaches testing subjects that include Caucasian and African-Americans and germline genetic testing of DDR genes including BRCA1 and PMS2.
Given the prior art teaches DDR genes with pathogenic mutations in prostate cancer, it would have been prima facie obvious to the ordinary artisan at the time the invention was made to include additional patient populations including patients of African descent in the patient analysis of Castro for a robust analysis of pathogenic mutations in DDR genes in patients with prostate cancer. The skilled artisan would have been motivated with a reasonable expectation of success that pathogenic DDR mutations could be assayed in different patient populations including patients of African descent, as taught by Moses. Additionally the skilled artisan would have had a reasonable expectation of success that mutations in DDR genes, including BRCA1 could be identified in subjects with African decent because Moses teaches identifying BRCA1 pathogenic mutations in African subjects with prostate cancer.
Claim 23 is rejected under 35 U.S.C. 103 as being unpatentable over Nombela (Cancers, 2019, vol 11, 352, pp 1-15) in view of Moses (J. Clinical Oncology, 2018, vol 36, no 6, pp 1-2).
Nombela teaches assaying a sample and identifying germline DDR mutations (see study design and patients). Nombelo teaches DDR gene screened for mutation in prostate cancer studies by assaying a prostate cancer sample to determine germline mutations in BRCA1, PMS2, RAD51, RAD54B. and RAD54L (see table 1). Therefore Nombela teaches assaying a biological sample to determine if the sample has a pathogenetic mutation in BRCA1, PMS2, RAD51, RAD54B and RAD54L and a patient is identified with prostate cancer. Nombela does not teach patients that are African descent.
However Moses teaches prostate cancer patients with metastases or strong family history of cancer are at higher risk of germline mutations in DDR genes. Moses teaches testing subjects that include Caucasian and African-Americans and germline genetic testing of DDR genes including BRCA1 and PMS2.
Given the prior art teaches DDR genes with pathogenic mutations in prostate cancer, it would have been prima facie obvious to the ordinary artisan at the time the invention was made to include additional patient populations including patients of African descent in the patient analysis of Nombela for a robust analysis of pathogenic mutations in DDR genes in patients with prostate cancer. The skilled artisan would have been motivated with a reasonable expectation of success that pathogenic DDR mutations could be assayed in different patient populations including patients of African descent, as taught by Moses. Additionally the skilled artisan would have had a reasonable expectation of success that mutations in DDR genes, including BRCA1 could be identified in subjects with African decent because Moses teaches identifying BRCA1 pathogenic mutations in African subjects with prostate cancer.
Response to Arguments
The response addresses each of the rejections above on pages 12-14 of the remarks. The response asserts the same traversal for each of the rejections. The response asserts that each of the primary references fail to assaying a plurality of genes comprises BRCA1, PMS2, RAD51, RAD54B, and RAD54L and nothing in each of the references would motivate a person of ordinary skill in the art to select Applicants five gene panel from the genes disclosed by Castro, Nombela, or Matugushi. As addressed in the previous response above, the claims are not limited to only a five gene panel, the claims recites plurality of genes comprising BRCA1, PMS2, RAD51, RAD54B, and RAD54L and recite assaying a plurality of genes, nothing in the claims limit the assaying step to only BRCA1, PMS2, RAD51, RAD54B, and RAD54L as such each of Castro, Nombela, and Matugushi teach assaying a plurality of genes comprising BRCA1, PMS2, RAD51, RAD54B, and RAD54L and Moses renders obvious including subjects of African descent. For these reasons and reasons of record these rejections are maintained.
New Grounds of Rejection
Claim Rejections - 35 USC § 112(a)
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, 8, 20, 23-32 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 is a new matter rejection.
Claim 1 recites a method of identifying and managing a subject having a predisposition for developing prostate cancer, the method comprising monitoring the subject identified as having prostate cancer predisposition for development of prostate cancer wherein the monitoring comprises PSA testing. The specification discloses a method of monitoring a response to therapy and increasing the frequence of monitoring the subject for development of prostate cancer or a more aggressive form of prostate cancer (see para 139) however the specification does not disclose monitoring that comprises PSA testing. The specification teaches determining whether the presence of certain DDRG mutations identify a patient having an increased risk of biochemical recurrence of prostate cancer by measuring PSA levels (see example 2) however the specification only measures PSA levels with respect to a biochemical recurrence of prostate cancer or to determine biochemical reaction. While the specification addresses PSA levels with respect to prostate cancer (see para 6 and 7), this does not disclose monitoring that comprises PSA testing in a subject identified as having predisposition to prostate cancer by assaying a plurality of genes, as recited in the claims. There is no support in the disclosure of monitoring subject identified as having prostate cancer predisposition for development of prostate cancer comprising PSA testing and the subject identified as predisposition is identified by mutations in BRCA1, PMS2, RAD51, RAD54B, and RAD54L. The specification does provide support for identifying a patient as having an increased risk of biochemical recurrence of prostate cancer by measuring PSA (see example 2) but not for the genus claimed.
Claim Rejections - 35 USC § 112(b)
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 3, 5 and 60 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 3 recites the limitation "the subject identified as having the prostate cancer predisposition for development of prostate cancer" in lines 8-9 of the claim. There is insufficient antecedent basis for this limitation in the claim. Claim 3 does not require identifying a subject as having the prostate cancer predisposition for development of prostate cancer. It is unclear which subjects are treated as treating requires a subject identified and the claim does not require identifying any subjects. Additionally the preamble recites treat a subject with prostate cancer with the claimed step reciting assaying each of a plurality of genes …obtained from the subject and treating the subject identified as having prostate cancer predisposition. It is unclear who is being treated as the assaying step requires a sample from a subject who has prostate cancer but then the treating step recites a subject identified as having prostate cancer predisposition. It is unclear if the treatment step is treating a different subject than the assaying step.
Claim Rejections - 35 USC § 103
Claims 59-61 are rejected under 35 U.S.C. 103 as being unpatentable over Nombela (2019) and Castro (2019).
Nombela teaches assaying a sample and identifying germline DDR mutations (see study design and patients). Nombelo teaches DDR gene screened for mutation in prostate cancer studies by assaying a prostate cancer sample to determine germline mutations in BRCA1, PMS2, RAD51, RAD54B. and RAD54L (see table 1). Nombela teaches monitoring PSA levels in BRCA2 carriers (see pg. 6). Therefore Nombela teaches assaying a biological sample to determine if the sample has a pathogenetic mutation in BRCA1, PMS2, RAD51, RAD54B and RAD54L and a patient is identified with prostate cancer and monitoring PSA levels. Nombela teaches identifying at least one pathogenic mutation in BRCA1 and treating patients which includes surgery and radiotherapy (see 3.1) Nombela further teaches mutations in BRCA and selecting platinum based and PARPi in prostate cancer (see 3.4). Nombela teaches DDR genes screened for mutations in mCRPC studies (see table 1). Nombela teaches sequencing pathogenic variants and validating using PCR or ligation dependent probe amplification (see germline variant analyses). Nombela teaches one set of DDR genes comprises 20 genes. Nombela teaches germline mutations in men with metastatic prostate cancer revealed 11.8% had mutation in one of the DDR genes analyzed. Nombela teaches screening studies in groups with different genetic backgrounds and accurate classification of variants are needed for precise estimation of prevalence of mutations in DDR genes across population (see section 2). Nombela does not teach contacting a sample with a plurality of probes for detecting at least one pathogenic mutation in no more than 20 different genes.
Castro teaches identifying pathogenic mutations in 20 different genes including BRCA2 and RAD54L. Castro teaches sequencing for pathogenic mutations followed by validation using PCR or multiplex ligation dependent probe amplification.
It would have been prima facie obvious to one of ordinary skill in the art to reduce the 107 genes that were assayed to 20 genes in the method of Nombela and Castro. Nombela teaches a set of 20 genes identified by mCRPC and Castro teaches identifying pathogenic mutations in 20 DDR genes, the ordinary artisan would have been motivated to reduce the number of genes in the assay to decrease the time and resources used to determine to pathogenic genes and reduce from 107 genes to 20 genes to allow for more precise estimation of mutations in DDR genes across populations. In order to assay 20 genes, the ordinary artisan would have been motived to use a hybridization assay or PCR assay that includes probes for detecting the DDR genes as taught by Castro to validate variants using PCR or MLPA, both assays will include probes for detecting DDR genes. It is noted the claims do not require specific probes to specific or a specific combination of genes but contacting the biological sample with a plurality of probes for detecting a pathogenic gene mutation in more than 20 different genes. Nombela and Castro render obvious the claimed invention.
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.
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/SARAE L BAUSCH/ Primary Examiner, Art Unit 1699