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 .
Any rejection not reiterated was overcome by amendment and argument as set forth in the response filed 7/7/2026.
New grounds of rejection are set forth herein.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings. See figure 5B.
Required response – Applicant must provide:
Replacement and annotated drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers into the Brief Description of the Drawings, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application No. 62/323547 and 62/480288, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. The claims are not entitled to priority the provisional applications because the Provisionals do not teach "the barcodes comprise a random molecular barcode" and the provisional applications do not teach barcoding DNA. Although 63/323574 teaches distinguishing DNA and RNA derived signals by barcoding and reverse transcribing RNA in a single step before library preparation and sequencing, ¶0023, the provisional application does not each that the barcode is a “random” molecular barcode, and the provisional does not mention also barcoding DNA as required by instant claim 1.
The filing date for the instant claims is the actual filing date, namely 4/16/2017.
Claim Rejections - 35 USC § 112
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 1-5, 9, 11-13, and 15-16 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.
The recitation “the barcodes” in line of part(b) of claim 1 lacks proper antecedent basis because it is not clear which barcodes, the ones on the DNA molecules or the RNA molecules must comprise “a random molecular barcode.” Furthermore, it is not clear what it means for a barcode to be a “random molecular barcode.” It is not clear what distinguishing feature must exist in a barcode to identify it as “random” or as “molecular”. The specification does not provide definition for this phrase and there is no art accepted meaning of the phrase.
It is unclear what it means when claim 11 recites the mutation is “AR-FL.” This term is not defined in the disclosure and in the prior art it is used to refer to the full length androgen receptor transcript. The specification does not clarify the matter because it refers to AR-FL as “WT” which is understood to mean wild-type. Therefore, it is unclear what it means to require that the mutation is “wild-type” since these two phrases are contradictory.
Any claim not enumerated is rejected because it depends from claim 1 and incorporates the indefiniteness in that claim.
Claim Rejections - 35 USC § 103
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.
Claim(s) 1, 2, 3, 5, 9, 11, 12, 13, and 15 is/are rejected under 35 U.S.C. 103 as being unpatentable over Qu et al. (Sci. Rep. 5, 7654; DOI:10.1038/srep07654 (2015)), Usher et al. (J Clin Oncol 34, e16613, May 20, 2016) in view of Reuter et al. (Nature Methods, Vol. 13, Nol. 11, November 2016).
Qu et al. teaches that AR-V7 plays an essential role in the development and progression of castration-resistant prostate cancer (CRPC), see abstract. Thus, the reference teaches that detecting AR-V7 expression is an indicator of CRPC in a patient.
Qu et al. does not teach detecting AR-V7 in a biofluid sample that comprises cfDNA and cfRNA.
Usher teaches isolating plasma from prostate cancer patients, extracting RNA, reverse transcribing and analyzing by quantitative RT-PCR. Usher demonstrates that AR-V7 was detected at the frequency consistent with previous findings. Plasma is inherently a sample that comprises cfDNA and cfRNA.
Neither Qu nor Usher teach the methodology recited in instant claim 1 wherein assaying a biofluid comprises barcoding the cell-free DNA molecules and the cell-free RNA molecules, or derivatives thereof to generate barcoded nucleic acids, wherein the barcodes comprise a random molecular barcode, and performing a sequencing assay on said barcoded nucleic acids to generate sequencing reads.
Reuter et al. teach a method for simultaneous single-tube sequencing of DNA and RNA from a sample in a single workflow. DNA and RNA are isolated simultaneously in a total nucleic acid isolation step. Tagmentation is used to attach a unique sequence to DNA molecules, and RNA adapter ligation is used to attach a unique sequence to RNA molecules. In this workflow, the different RNA and DNA adapter sequences are considered “random molecular identifiers” because they are identifiers that identify molecules- DNA or RNA. Here “random” is a limitation that describes how the identifiers were made but does not describe any clear structure of the identifiers. To accomplish the action required by the claim, namely, to separate the DNA reads from the RNA reads, only two total adapter sequences are required. By its very nature the descriptor “random” means that anything could be selected, and so the four sequences taught by Reuter are considered “random molecular identifiers.” Reuter further teaches that the DNA and RNA are separated by sequence alignment using the distinct adapters. See Figure 1a, and throughout.
Taking the teachings of the references together, it would have been obvious to have modified the method taught by Qu et al. to have detected the presence of AR-V7 in plasma samples from patients having prostate cancer to detect the splice variant that was known to have a role in the development of castrate resistance, and thereby detect castration resistant prostate cancer in a patient. One would have been motivated to test plasma samples as a non-invasive sample for detecting the variant. Furthermore, it would have been obvious to use the sequencing method taught by Reuter et al. because this would have allowed for the analysis of both DNA and RNA simultaneously. One would have been motivated to use the sequencing method taught by Reuter because it allows detection of transcript and genomic sequences simultaneously and it was well known at the time of the invention that prostate cancer could have splice mutations or genomic mutations and a method which allowed screening of DNA and RNA would have been useful for detecting both cancer related mutations and expression variations.
Regarding claim 11, the claim is included in this rejection because while the claim further limits the mutation, the claim still does not require detecting the mutation as the mutation detection is optional in claim 1.
Regarding claim 15, Reuter teaches differential adapter PCR of complementary DNA, thus teaches analyzing the cDNA molecules using polymerase chain reaction. See figure 1a.
Claim(s) 1, 2, 3, 4, 5, 9, 11, 12, 13, and 15 is/are rejected under 35 U.S.C. 103 as being unpatentable over Qu, Usher and Reuter as applied to claims 1, 2, 3, 5, 9, 11, 12, 13, and 15 above, and further in view of Albitar et al. (Journal of Cancer. 2/2/2016; 7(3):297-303).
The teachings of Qu, Usher and Reuter are given previously in this Office action and are fully incorporated here.
These do not teach a method wherein the biofluid sample is urine.
Albitar teaches that prostate cancer biomarkers can be found in urine and plasma, and that employing these samples is non-invasive and can be used for PCa screening and active surveillance (p. 302, 2nd column).
It would have been prima facie obvious to have also analyzed the nucleic acids in urine alongside the plasma samples to have provided a more complete assay for detecting androgen receptor splice variants and mutations. Albitar exemplifies the cell free nucleic acids in urine can be used for PCa biomarker screening and active surveillance and it would have been obvious to have employed this additional non-invasive technique in the screening of AR genes in prostate cancer patients.
Claim(s) 1, 2, 3, 5, 9, 11, 12, 13, 15 and 16 is/are rejected under 35 U.S.C. 103 as being unpatentable over Qu, Usher and Reuter as applied to claims 1, 2, 3, 5, 9, 11, 12, 13, and 15 above, and further in view of Oudes et al. (BMC Cancer 2005, 5:86; 12 pages).
The teachings of Qu, Usher and Reuter are given previously in this Office action and are fully incorporated here.
These do not teach a method wherein the cDNA molecules are analyzed using an array-based technology.
Oudes et al. teach analysis of expression by performing Affymetrix GeneChip array analysis, sequencing, and RT-PCR. The RT-PCR was used to verify array results.
Oudes teaches that a combination of profiling technologies such as DNA array and sequencing provides a more robust means to assess the expression profile of an RNA sample than any single technique (Abstract and discussion).
It would have been obvious to have modified the method taught by Qu, Usher and Reuter by also testing for expression of cfRNA by analyzing derived cDNA as taught using PCR and array based technology by Oudes et al. because Oudes et al. specifically suggests that using more than one technique for expression profiling yields more robust results.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 2, 3, 4, 5, 9, 11, 12, and 13 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-28 of U.S. Patent No. 11174503 in view of Qu and Usher et al.
The issued claims teach a method that includes assaying a biofluid sample for an AR-V, wherein the biofluid sample comprises cell free DNA and cell free RNA. The reference teaches the assaying includes barcoding cell-free DNA and RNA molecules wherein the barcodes comprise a random molecular barcode and performing a sequencing assay on said barcoded nucleic acids, to generate sequencing reads. The issued claims teach separating said sequencing reads into DNA-derived reads and RNA-derived reads. The issued claims teach detecting a cancer associated gene associated with prostate cancer. See issued claims 1, 13, 14, 18, and issued claim 20.
The issued claims teach the presence of an genetic alteration is indicative of a presence or absence of disease, wherein the disease is cancer, wherein the generic alteration occurs in a cancer-associated gene. See claims 7-9. The issued claims teach the disease is prostate cancer, and the genetic variant is a splice variant of androgen receptor gene, see claims 18 and 20.
The issued claims further teach extracting both DNA and RNA molecules simultaneously. See claim 11.
The issued claims teach that the biofluid can be plasma or urine, see claim 6 and claim 24.
Regarding the limitation that the barcodes are “random” there is nothing in the claim that distinguishes the molecular barcodes of the issued claims from the “random molecular barcodes” of the instant claims. Both are sufficient to separate DNA and RNA reads.
The issued claims do not teach detecting castration resistant prostate cancer in said subject based at least in part on the presence of the AR-V, nor do they teach detecting AR-V7.
Qu et al. teaches that AR-V7 plays an essential role in the development and progression of castration-resistant prostate cancer (CRPC), see abstract. Thus, the reference teaches that detecting AR-V7 expression is an indicator of CRPC in a patient.
Qu et al. does not teach detecting AR-V7 in a biofluid sample that comprises cfDNA and cfRNA.
Usher teaches isolating plasma from prostate cancer patients, extracting RNA, reverse transcribing and analyzing by quantitative RT-PCR. Usher demonstrates that AR-V7 was detected at the frequency consistent with previous findings. Plasma is inherently a sample that comprises cfDNA and cfRNA.
It would have been obvious to have modified the issued claims to detect AR-V7 in biological samples for detecting the presence of castration resistant prostate cancer. One would have been motivated to do so by the express teaching in the issued claims that the methods can be used to detect prostate cancer and that the methods can be used to detect AR splice variant, in particular.
Claims 1, 2, 3, 4, 5, 9, 11, 12, 13, 15, and 16 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-28 of U.S. Patent No. 11174503 in view of Qu and Usher et al. and Oudes et al. (BMC Cancer 2005, 5:86; 12 pages)
The teachings of the issued claims in view of Qu and Usher are given previously and are incorporated here. Regarding claims 15 and 16, the issued claims do not teach analyzing cDNA by PCR or an array.
Oudes et al. teach analysis of expression by performing Affymetrix GeneChip array analysis, sequencing, and RT-PCR. The RT-PCR was used to verify array results.
Oudes teaches that a combination of profiling technologies such as DNA array and sequencing provides a more robust means to assess the expression profile of an RNA sample than any single technique (Abstract and discussion).
It would have been obvious to have modified the method taught by the issued claims in view of Qu and Usher by also testing for expression of cfRNA by analyzing derived cDNA as taught using PCR and array based technology by Oudes et al. because Oudes et al. specifically suggests that using more than one technique for expression profiling yields more robust results.
Claims 1, 2, 3, 4, 5, 9, 11, 12, and 13 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11702702.
The issued claims teach a method that includes assaying a biofluid sample for an AR-V, wherein the biofluid sample comprises cell free DNA and cell free RNA. The reference teaches the assaying includes barcoding cell-free DNA and RNA molecules wherein the barcodes comprise a random molecular barcode and performing a sequencing assay on said barcoded nucleic acids, to generate sequencing reads. The issued claims teach separating said sequencing reads into DNA-derived reads and RNA-derived reads. The issued claims teach detecting a cancer associated gene associated with prostate cancer. See issued claims 1, 3, 9, .
The issued claims teach the presence of an genetic alteration is indicative of a presence or absence of disease, wherein the disease is cancer, wherein the generic alteration occurs in a cancer-associated gene. See claims 9-11. The issued claims teach the disease is castration resistant prostate cancer, and the genetic variant is a splice variant of androgen receptor gene or a mutated AR, including those mutations and splice variants recited in the instant claims, see claims 15-18.
The issued claims further teach extracting both DNA and RNA molecules simultaneously. See claim 20.
The issued claims teach that the biofluid can be plasma or urine, see claim 6.
Regarding the limitation that the barcodes are “random” there is nothing in the claim that distinguishes the molecular barcodes of the issued claims from the “random molecular barcodes” of the instant claims. Both are sufficient to separate DNA and RNA reads.
The prohibition against double patenting does not apply in this instance because the claims of the application under examination and the claims of the other patent are not consonant with the restriction requirement made by the examiner since the claims have been changed in material respects from the claims at the time the requirement was made. The line of demarcation was not maintained. See MPEP 804.01(B).
Claims 15 and 16 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11702702 in view Oudes et al. (BMC Cancer 2005, 5:86; 12 pages)
The teachings of the issued claims are given previously and are incorporated here. Regarding claims 15 and 16, the issued claims do not teach analyzing cDNA by PCR or an array.
Oudes et al. teach analysis of expression by performing Affymetrix GeneChip array analysis, sequencing, and RT-PCR. The RT-PCR was used to verify array results.
Oudes teaches that a combination of profiling technologies such as DNA array and sequencing provides a more robust means to assess the expression profile of an RNA sample than any single technique (Abstract and discussion).
It would have been obvious to have modified the method taught by the issued claims in view of Qu and Usher by also testing for expression of cfRNA by analyzing derived cDNA as taught using PCR and array based technology by Oudes et al. because Oudes et al. specifically suggests that using more than one technique for expression profiling yields more robust results.
The prohibition against double patenting does not apply in this instance because the claims of the application under examination and the claims of the other patent are not consonant with the restriction requiement made by the examiner since the claims have been changed in material respects from the claims at the time the requirement was made. The line of demarcation was not maintained. See MPEP 804.01(B).
Claims 1, 2, 3, 4, 5, 9, 11, 12, and 13 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-29 of U.S. Patent No. 11913063 in view of Qu and Usher et al.
The issued claims teach a method that includes assaying a biofluid sample for an AR-V, wherein the biofluid sample comprises cell free DNA and cell free RNA. The reference teaches the assaying includes barcoding cell-free DNA and RNA molecules wherein the barcodes comprise a random molecular barcode and performing a sequencing assay on said barcoded nucleic acids, to generate sequencing reads. The issued claims teach separating said sequencing reads into DNA-derived reads and RNA-derived reads. The issued claims teach detecting a cancer associated gene associated with prostate cancer. See issued claims 1-5, 19-20, 21-23, 13, 14, 18, and issued claim 20.
The issued claims teach the presence of an genetic alteration is indicative of a presence or absence of disease, wherein the disease is cancer, wherein the generic alteration occurs in a cancer-associated gene. See issued claims 14-15 and 17. The issued claims teach the disease is prostate cancer, and the genetic variant is a splice variant of androgen receptor gene, specifically AR-V7, see issued claims 21 and 22.
The issued claims further teach extracting both DNA and RNA molecules simultaneously. See issued claim 27.
The issued claims teach that the biofluid can be plasma or urine, see claim 6 and claim 24.
Regarding the limitation that the barcodes are “random” there is nothing in the claim that distinguishes the molecular barcodes of the issued claims from the “random molecular barcodes” of the instant claims. Both are sufficient to separate DNA and RNA reads.
The issued claims do not teach detecting castration resistant prostate cancer in said subject based at least in part on the presence of the AR-V.
Qu et al. teaches that AR-V7 plays an essential role in the development and progression of castration-resistant prostate cancer (CRPC), see abstract. Thus, the reference teaches that detecting AR-V7 expression is an indicator of CRPC in a patient.
Qu et al. does not teach detecting AR-V7 in a biofluid sample that comprises cfDNA and cfRNA.
Usher teaches isolating plasma from prostate cancer patients, extracting RNA, reverse transcribing and analyzing by quantitative RT-PCR. Usher demonstrates that AR-V7 was detected at the frequency consistent with previous findings. Plasma is inherently a sample that comprises cfDNA and cfRNA.
It would have been obvious to have modified the issued claims to detect AR-V7 in biological samples for detecting the presence of castration resistant prostate cancer. One would have been motivated to do so by the express teaching in the issued claims that the methods can be used to detect prostate cancer and that the methods can be used to detect AR splice variant, in particular.
Claims 1, 2, 3, 4, 5, 9, 11, 12, 13, 15, and 16 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-29 of U.S. Patent No. 11913063 in view of Qu and Usher et al. and Oudes et al. (BMC Cancer 2005, 5:86; 12 pages)
The teachings of the issued claims in view of Qu and Usher are given previously and are incorporated here. Regarding claims 15 and 16, the issued claims do not teach analyzing cDNA by PCR or an array.
Oudes et al. teach analysis of expression by performing Affymetrix GeneChip array analysis, sequencing, and RT-PCR. The RT-PCR was used to verify array results.
Oudes teaches that a combination of profiling technologies such as DNA array and sequencing provides a more robust means to assess the expression profile of an RNA sample than any single technique (Abstract and discussion).
It would have been obvious to have modified the method taught by the issued claims in view of Qu and Usher by also testing for expression of cfRNA by analyzing derived cDNA as taught using PCR and array based technology by Oudes et al. because Oudes et al. specifically suggests that using more than one technique for expression profiling yields more robust results.
Rule 105 Requirement for Information
Applicant and the assignee of this application are required under 37 CFR 1.105 to provide the following information that the examiner has determined is reasonably necessary to the examination of this application.
The Jia abstract entitled “Integrated genomic cfDNA/cfRNA profiling for AR-V7 liquid biopsy test in prostate cancer” is attached to this Office action. The publication is dated July 1, 2017. However, the meeting date was April 1-5, 2017.
In response to this requirement, please provide answers to each of the following interrogatories eliciting factual information:
Was the abstract released publicly before or at the meeting? If so, what date?
Was a poster or presentation given at the meeting? If so provide any slides or poster that were presented, and the date that they were publicly presented.
The timing fee and certification requirements of 37 CFR 1.97 are waived for those documents submitted in reply to the requirement. This waiver extends only to those documents within the scope of this requirement under 37 CFR 1.105 that are included in the applicant’s first complete communication responding to this requirement. Any supplemental replies subsequent to the first communication responding to this requirement and any information disclosures beyond the scope of this requirement under 37 CFR 1.105 are subject to the fee and certification requirements of 37 CFR 1.97 where appropriate.
The applicant is reminded that the reply to this requirement must be made with candor and good faith under 37 CFR 1.56. Where the applicant does not have or cannot readily obtain an item of required information, a statement that the item is unknown or cannot be readily obtained may be accepted as a complete reply to the requirement for that item.
This requirement is an attachment of the enclosed Office action. A complete reply to the enclosed Office action must include a complete reply to this requirement. The time period for reply to this requirement coincides with the time period for reply to the enclosed Office action.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Sun et al. teaches castration resistance in human prostate cancer is conferred by the ARV567ES gene splice variant. Sun et al. J Clin Invest. 2010;120(8):2715–2730.
Azad teaches detecting mutations in cfDNA samples from prostate cancer patients, including detecting F876L in a patient (see Table 2). Azad et al. Clin Cancer Res; 21(10); 2315–24. _2015
Enderle et al. (US 20200149036) teaches barcoding RNA while producing cDNA and then sequencing a combined cDNA with DNA mixture and separating reads. See Figure 1.
Kivioja et al. teach counting absolute numbers of molecules using unique molecular identifiers. Kivioja et al. Nature Methods, 2012, Vol. 9, No. 1, pages 72-74 plus online methods.
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 at (571)-272-3157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Juliet Switzer
Primary Examiner
Art Unit 1682
/JULIET C SWITZER/ Primary Examiner, Art Unit 1682
