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 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 for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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.
Claims 32, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43-54 are rejected under 35 U.S.C. 103 as being unpatentable over You ([You et al. Pub. No.: US2018 0282817A1, PCT filing date of Priority date of 05 October 2015) in view of Parker (Parker et al. American Society of Clinical Oncology; 2009; 27; 8: 1160-1167) and Bagrodia et al. (Indian J Urol 2009;25:169-76.), and optionally further in view of Steelman (PG Pub No: US20200181710A1 with Priority date of 23 December 2015), Damrauer et al. (PNAS; 2014; 111; 8: 3110–3115).
You teaches a method for classifying human prostate cancer into prostate cancer subtype (PCS) of PCS1, PCS2 or PCS3 via gene expression levels of more than 400 genes (see abstract, Figure 4 C, Figure 5 A, Table 1, para 0009, para 0070, para 0073, para 0118, Figure 1A, Figure 2C, Figure 4C). You teaches measuring/detecting gene expression levels of 23 genes out of 50 recited genes in a biological sample from a prostate cancer subject. The genes are CDC20, KIF2C, NUF2, CENPF, EXO1, UBE2T, RRM2, CCNB1, GPR160, PTTG1, ANLN, MELK, CEP55, MKI67, TMEM45B, KRT5, FOXA1, CDC6, BIRC5, KRT17, TYMS, SLC39A6 and UBE2C (see Table 1, Figure 2 C, Figure 4 C, para 0009, para 0070, para 0073).
You teaches obtaining a sample from a subject having a prostate cancer and assaying the sample to detect changes in gene expression of one or more genes in the sample (see para 0009-0012, para 0049, para 0066-0069, para 0166-0169, claims 1, 17, and 31). You teaches using RNA expression data, that is measuring the level of an RNA transcript, to categorize prostate cancer tumors into 3 distinct subtypes, using nucleic acids as detection agents to detect the target in the sample and determining mRNA levels in the sample (see para 0006, para 0116-0117, para 0119- 0121). Thus, the method of You includes extracting nucleic acids from the biological sample obtained from prostate cancer subject because this method step of extracting nucleic acid is required to further process the detection assay to determine mRNA levels.
You further teaches determining the presence of an expression pattern of a plurality of genes associated with the subtype of in the sample based on the detected changes (see para 0009-12, para 0049, para 0066-0069, para 0165-0169, claims 1, 17, and 31). Particularly, You teaches detecting genes expression in the tissue samples of prostate cancer patients and assigning the prostate cancer into subtype as PCS1, PCS2 or PCS3 using a set of pathways- classifier or a set of genes-classifier (see para 0016-0019, Figure 2, Figure 4-5, para 0066-0069, para 0165-0169).
You further teaches determining whether the PCS categories reflect luminal or basal types of the prostate epithelium through detected gene expressions (see para 0164-0165). For example, You teaches observing an association between a combination of gene-expressions (a mean expression of group of genes) comprising MKI67 that is known to be luminal prostatic cells (luminal subtype). You teaches observing a strong association between luminal genes with PCS1 and PCS2; and basal genes and PCS3 (para 0165, Table 7). Thus, You teaches two luminal subtypes of prostate cancers (i.e. PCS1 and PCS2) and one basal subtype of prostate cancer (i.e. PCS3). This is considered three prostate cancer subtypes with a luminal A subtype, a luminal B subtype and a basal subtype prostate cancer.
Thus, You teaches subtyping the prostate cancer of the subject according to a genomic subtyping classifier based on the levels of expression of the plurality of genes, wherein said subtyping comprises assigning the prostate cancer to one of three subtypes selected from the group consisting of a luminal A subtype, a luminal B subtype, and a basal subtype.
You teaches a method for treating a subject with prostate cancer that comprises a series of method steps. You teaches treating the PCS1 and PCS2 patients (i.e. luminal A and B cancers) with chemotherapy (para 84-85, 91). Regarding claims 51-54 these claims further limit certain treatment options, but depend ultimately from claims where these options are not required, and the claims do not require that “surgery” or “radiation therapy” are delivered.
You teaches that the sample can be a biopsy or whole blood or urine among other options (para 30).
You teaches that gene expression can be measured by PCR or microarray, among other options (para 116). PCR employs nucleic acid primers, inherently.
You does not teach measuring 27 recited genes out of 50 genes in the claim for subtyping of the prostate cancer of the subject, although You teaches measuring multiple genes correspond to prostate cancer (see Table 1).
Parker teaches a method of using a 50-gene subtype predictor using microarray and quantitative reverse transcriptase polymerase chain reaction (RT-PCR) data for subtyping in likelihood of breast cancer, for example, subtypes luminal A, luminal B, HER2-enrihced and basal-like (see abstract, p 1161 col 1-2, Table 1). Particularly, Parker teaches extracting RNA from the samples obtained from breast cancer patient, measuring gene expression levels and identifying the intrinsic subtypes in the method (see p 1161 col 1-2, Figure 1). Parker teaches using the 50- gene classifier (PAM50) (see Appendix Figure A3) to assign the subtype classification to determine the significant of the intrinsic subtypes in untreated patients and in patients receiving neoadjuvant chemotherapy (see p 1161 para 6 through p 1162 col 1, Figure 1).
As shown in Figure A3 (see below), the 50-gene classifier includes all the recited 50 genes, whereas recited NUF2 as CDCA1, and recited NDC80 as KNTC2.
PNG
media_image1.png
597
587
media_image1.png
Greyscale
Therefore, it would have been prima facie obvious prior to one having skill in the art prior to the effective filing date of the claimed invention to have modified the method of You, so as to have used a genomic subtyping classifier with 50 genes as taught by Parker. You teaches measuring and analyzing gene expression levels of hundreds of genes for molecular classification of prostate cancer; and exemplifies using a 37-gene classifier (including 23 recited genes) to assign subtypes to the specimens in the method (see para 0149-0153, Table 1-2). Parker exemplifies using a 50-gene classifier (including 23 recited genes) to assign subtypes to the specimens in predicting the prognosis of breast cancer, as described above. Parker teaches that the intrinsic subtype and risk predictors based on the PAM50 gene set added significant prognostic and predictive value to pathologic staging, staging, histologic grade, and standard clinical molecular markers (see p 1165 col 1 para 2). Thus, it would have been obvious to one having skill in the art to have used a gene classifier having a group of genes (i.e. PAM50) known for its significant prognostic and predictive value in assigning the subtypes for cancer, as taught by Parker in the method of You, in order to provide the method that is capable assessing the likelihood of prostate cancer or the likelihood of efficacy of the treatment of prostate cancer through molecular classification of prostate cancer with high sensitivity and specificity.
With regard to the claim requirement to deliver an anti-cancer treatment that does not comprise androgen deprivation, You et al. explicitly teaches embodiments that include treating PCS1 and PCS2 patients with chemotherapy, as noted above. Furthermore, before the effective filing date, it was well known that ADT included adverse health effects for patients, including impact on health-related quality of life, sexual dysfunction, vasomotor symptoms, endocrine dysfunction, cardiovascular phenomena (diabetes, MI, sudden cardiac death), and bone loss and fractures, Bagrodia et al. (Table 1 and throughout).
Therefore, given that You et al. suggests chemotherapy as an option for treatment of luminal patients (i.e. PCS1 and PCS2) and that there were known reasons one might decide against ADT, it would have been prima facie obvious to treat luminal A patients identified by the PAM50 with chemotherapy, and not with ADT, as it was recognized that ADT also comes with risks and a patient may have been more willing to accept the risks of chemotherapy than ADT.
Additionally, the artisan would have found it obvious to have used the genes includes in PAM50 classifier for subtyping the prostate cancer because prior art suggests that the PAM50 classifier could be applied to cancers other than breast cancer.
For example, Steelman teaches a method of detecting a number of biomarkers (including all the genes of PAM50 set) which are associated with prostate cancer (see para 0008-0009 and Table 21 page 13). Steelman teaches performing subtyping of the cancer (e.g. breast cancer) using classifiers (e.g. PAM50) (see para 0056, para 112, para 236-239, para 310, para 328, para 352, para 0141, para 0497-0498, Table 18, Table 21 page 13). Steelman suggests the applicability of the method for prostate cancer (para 0328, claims 1, 25, 27, 37, 60, 62).
Damrauer teaches methods of intrinsic molecular subtyping of high-grade bladder cancer, as luminal and basal-like subtypes via gene expression data in tumor samples using microarray analysis and PAM50 classier (see abstract, p 3110 col 2 para 1, p 3111 col 1-2, Figure 4). Damrauer et al. further teaches that the identified luminal and basal-like subtypes reflect the luminal and basal-like molecular subtypes of breast cancer which was also analyzed the subtypes using the PAM50 classifier (see abstract, p 3112 col 1-2).
Claim(s) 32-54 is/are rejected under 35 U.S.C. 103 as being unpatentable over Feng et al. 2017, Journal of clinical Oncology, Volume 35(6) Supplement, 20 Feb 2017, p. 3 in view of You et al. AND
Claim(s) 32-54 is/are rejected under 35 U.S.C. 103 as being unpatentable over Feng et al. February 16, 2017, Liminal and basal subtyping of prostate cancer, PowerPoint presentation, 2017 Genitourinary Cancers Symposium, 16pp. in view of You et al.
The two Feng disclosures are substantially duplicative.
Both Feng et al. references teach a method which includes obtaining the expression level in a biological sample from a subject having prostate cancer for each of the genes listed in the claims. Specifically, the references teach applying the PAM50 classifier to identify subtypes of prostate cancer, including identifying Luminal A patients. The PAM50 classifier inherently includes the genes recited in the claims.
The Feng references further teach that only Luminal B prostate cancer was significantly associated with post-operative response to ADT.
The Feng references teach using a microarray for detecting gene expression of the PAM50 target genes, and a microarray inherently employs oligonucleotide probes.
The Feng references do not specifically teach treating Luminal A cancer patients with chemotherapy, nor does Feng teach all of the limitations of the dependent claims with regard to sample type and technique.
The teachings of You are given previously in this Office action and are fully incorporated here. You teaches treating luminal type prostate cancer with chemotherapy. Additionally, You teaches using biopsy samples as well as urine or blood samples for gene expression analysis to classify prostate cancer into one of three categories.
It would have been obvious to have treated patients identified as being Luminal A with chemotherapy since You specifically provides an embodiment where luminal patients are treated with chemotherapy, and Feng teaches that only Luminal B patients were significantly associated with response to ADT. Furthermore, it would have been obvious to apply the method taught by Feng to urine, biopsy and blood samples as You teach these as appropriate samples for classifying prostate cancers by gene expression analysis.
NOTE: Affidavits or declarations, such as those submitted under 37 CFR 1.130, 1.131 and 1.132, filed during the prosecution of the prior application do not automatically become a part of this application. Where it is desired to rely on an earlier-filed affidavit or declaration, the applicant should make remarks of record in this application and include a copy of the original affidavit or declaration filed in the prior application.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Juliet Switzer whose telephone number is (571)272-0753. The examiner can normally be reached Monday to Thursday, 8:00 AM-3:30 PM.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Winston Shen can be reached on (571)-272-3157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/JULIET C SWITZER/Primary Examiner, Art Unit 1634
Prosecution Insights