DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
2. Applicant’s election without traverse of the species as recited in claim 34 in the reply filed on 12/11/2025 is acknowledged
3. Claims 21-53 are pending in the application. Claims 29-33 and 39-51 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Claims 21-28, 34-38 and 52-53 are currently under examination.
Claim Objections
4. Claim 21 is objected to because of the following informalities:
Claim 21, lines 3-4: “non-coding ribonucleic acid RNA molecules” should be changed to “non-coding ribonucleic acid (RNA) molecules” for more clarity.
Claim 21, last line: “outputting biomedical information of a subject” should be changed to “outputting biomedical information of [[a]] the subject” for more clarity.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
5. 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.
6. Claims 21-28, 34-38 and 52-53 are rejected 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 21 recites “wherein the plurality of genetic characteristics include nucleic acid molecules from at least one biological sample of a subject” (emphasis provided) at the end of step (a). It is not clear how “genetic characteristics” can include “nucleic acid molecules”, because “nucleic acid molecules” are genetic materials rather than genetic characteristics. Claims 22-28, 34-38 and 52-53, each of which depends from claim 21, are also rejected for the same reason.
In the interest of compact prosecution and for purposes of current examination, the wherein clause at the end of step (a) in claim 21 is being interpreted as “wherein the assay is designed to analyze nucleic acid molecules from at least one biological sample of a subject”.
7. The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), fourth paragraph:
Subject to the [fifth paragraph of 35 U.S.C. 112 (pre-AIA )], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
8. Claim 25 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 25, dependent from claim 24 which further depends from claim 21, recites “wherein the sequencing assay comprises generating nucleic acid sequence data from the at least one biological sample of a subject”. Since claim 21 recites “perform the assay on one or more biological samples from the subject to generate data” and claim 24 recites “wherein the assay comprises a sequencing assay”, the limitation(s) recited in the wherein clause of claim 25 is already recited in claims 21 and 24. Thus, claim 25 is of improper dependent form for failing to further limit the subject matter of the claim upon which it depends.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Double Patenting
9. 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.
10. Claims 21-28, 34-38 and 52-53 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-31 of U.S. Patent No. 10,450,611. Although the claims at issue are not identical, they are not patentably distinct from each other because claims 1-31 of U.S. Patent No. 10,450,611 teach or render obvious all the features as recited in instant claims 21-28, 34-38 and 52-53. Specifically, claims 1, 9 and 19 of U.S. Patent No. 10,450,611 teach all the steps and elements required by instant claim 21. In addition, the other features as recited in instant claims 22-28, 34-38 and 52-53 are also taught or rendered obvious by claims 1-31 of U.S. Patent No. 10,450,611.
Claim Rejections - 35 USC § 102
11. 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.
12. 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.
13. Claims 21-25, 28, 34-38 and 52-53 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Wellstein et al. (WO 2015/054220 A1).
Regarding claim 21
Wellstein et al. teach, throughout the whole document, a method for personalized genetic testing, comprising: (a) using a plurality of genetic characteristics to determine a nucleic acid configuration of an assay, wherein the plurality of genetic characteristics includes quantification of non-coding ribonucleic acid (RNA) molecules or micro-RNA (i.e., microRNA or miR) molecules which are at least partially tissue-type specific or cancer-type specific (e.g., quantification of “a panel of sixteen miRs that had been shown to be differentially expressed between colorectal cancer and normal colon tissues” as shown in Example 2 (see pages 37-38) and quantification of “760 miRs” as shown in Example 3 (see page 38) to select six miRs (see page 38, lines 18-22) to be used in the validation assay of Example 4 (see pages 38-39) or the diagnostic/prognostic assay as described in Example 6 (see pages 40-41)), which nucleic acid configuration includes nucleic acid sequences of a plurality of nucleic acid probe molecules (e.g., from the pilot studies of Examples 2-3, six miRs are selected (see page 38, lines 18-22) for the validation assay of Example 4 (see pages 38-39) or the diagnostic/prognostic assay as described in Example 6 (see pages 40-41), where the assay involves the use of nucleic acid primers for analyzing/quantifying the 6 miRs by qRT-PCR), and wherein the assay is designed to analyze nucleic acid molecules from at least one biological sample of a subject (see Examples 2-4 and 6 shown in pages 37-41; Figure 1A); (b) providing the plurality of nucleic acid probe molecules by (i) synthesizing the plurality of nucleic acid probe molecules, or (ii) selecting the plurality of nucleic acid probe molecules from a collection of nucleic acid probe molecules (see page 37, lines 17-18: “Primers for quantitative RT-PCR to specific miRs are commercially available”, meaning that the primers are synthesized by the commercial supplier(s) and that the primers are selected from a larger pool of commercially available nucleic acid primers for analyzing miRs); (c) using the plurality of nucleic acid probe molecules provided in (b) to perform the assay on one or more biological samples from the subject to generate data (see Examples 4 and 6 shown in pages 38-41; page 2, line 6 – page 4, line 18); and (d) based on the data of (c), outputting biomedical information (e.g., the measured levels of the 6 miRs and/or the corresponding diagnostic/prognostic result) of the subject (see Examples 4 and 6 shown in pages 38-41; page 2, line 6 – page 4, line 18).
Regarding claim 22
The method according to Wellstein et al., wherein the at least one biological sample comprises (i) tumor ribonucleic acid (RNA) or complementary DNA derived from the tumor RNA and/or (ii) cell-free RNA derived from blood plasma (see paragraph bridging pages 3-4: “…measuring in the biological material the levels of two or more microRNAs comprises measuring the levels of miR-15a, miR-103, miR-148a, miR-320a, miR-451 and miR-596. …the biological material is a biological fluid. …the biological fluid is selected from: blood plasma, blood serum”; page 21, lines 8-18: “In some embodiments, the biological material is a solid tissue sample, a bodily fluid sample, or circulating tumor cells. In some embodiments, the bodily fluid sample may be blood, plasma, …the solid tissue sample may be a formalin-fixed paraffin embedded tissue sample, …surgically removed tumor tissue, or a biopsy sample”).
Regarding claim 23
The method according to Wellstein et al., wherein synthesizing the plurality of nucleic acid probe molecules comprises using at least one array (see page 4, lines 5-8 and 28-33).
Regarding claims 24-25
The method according to Wellstein et al., wherein the assay comprises a sequencing assay (see page 20, lines 16-18), wherein the sequencing assay would necessarily generate nucleic acid sequence data from the at least one biological sample of a subject.
Regarding claim 28
The method according to Wellstein et al., wherein the biomedical information comprises a biomedical report (e.g., biomedical report with the measured levels of the 6 miRs and/or the corresponding diagnostic/prognostic result. See Examples 4 and 6 shown in pages 38-41; page 2, line 6 – page 4, line 18).
Regarding claims 34-35
The method according to Wellstein et al., wherein the biomedical report comprises reporting information of the subject that is predictive, prognostic, or diagnostic of a status or outcome of a disease or condition in the subject, wherein the predictive, prognostic, or diagnostic information of the biomedical report comprises a member selected from the group consisting of: diagnosing a disease or condition, identifying a disease or condition, determining the stage of a disease or condition, assessing the risk of a disease or condition, assessing the risk of disease recurrence (e.g., assessing/predicting the risk of cancer recurrence), assessing reproductive risk, assessing genetic risk to a fetus, assessing the efficacy of a drug, assessing risk of an adverse drug reaction, predicting optimal drug dosage, and predicting drug resistance (see Example 6 as shown in pages 40-41; page 2, line 6 – page 4, line 18).
Regarding claims 36-38
The method according to Wellstein et al., wherein the disease or condition comprises cancer, wherein the cancer comprises recurrent cancer (e.g., recurrent colorectal cancer), and wherein the cancer comprises a carcinoma (see page 2, line 6 – page 4, line 18; Examples 4-6 as shown in pages 38-41).
Regarding claim 52
The method according to Wellstein et al., wherein the plurality of genetic characteristics in (a) comprise locations in or regions of a genome (e.g., regions of a genome encoding the miRs), and wherein the plurality of nucleic acid probe molecules of the assay enrich (via amplifying with RT-PCR) or deplete (via hybridization with hybridization probes or an array) a nucleic acid mixture of nucleic acid molecules which include the locations or regions of the genome or portions thereof (see page 4, lines 5-8 and 28-33; Examples 1-6).
Regarding claim 53
The method according to Wellstein et al., wherein the plurality of nucleic acid probe molecules of the assay enriches (via amplifying with RT-PCR) or depletes (via hybridization with hybridization probes or an array) a nucleic acid mixture of nucleic acid molecules for target regions by hybridization or amplification (see page 4, lines 5-8 and 28-33; Examples 1-6).
Claim Rejections - 35 USC § 103
14. 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 of this title, 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.
15. 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.
16. Claims 26-27 are rejected under 35 U.S.C. 103 as being unpatentable over Wellstein et al. (WO 2015/054220 A1) as applied to claims 21-25, 28, 34-38 and 52-53 above, and further in view of Graybill et al. (Anal. Chem. 2016, 88:431-450, published on 10 December 2015).
Wellstein et al. teach the method of claims 21 and 24-25 as discussed above. Although Wellstein et al. teach that the levels of the microRNAs (miRs) may be determined by sequencing (see page 20, lines 16-18), Wellstein et al. do not specifically disclose the details as recited in claims 26-27.
However, Graybill et al., in reviewing the various art-recognized approaches for microRNA analysis, teach that “[t]hree major approaches are used at present to determine levels of miRNA expression: (1) reverse transcription-quantitative polymerase chain reaction (qRT-PCR), (2) hybridization-based microarrays, and (3) next generation high-throughput sequencing” (see page 433, column 2, paragraph 2), wherein the sequencing approach involves the use of primers for amplifying nucleic acid sequences to prepare cDNAs from the RNA-containing sample of interest using a reverse transcription process similar to qRT-PCR (see page 435, column 2, paragraph 2; Figure 3C), and wherein the sequencing assay is performed at a depth sufficient to determine which genes may benefit from having their relative number of sequencing reads increased or decreased (see page 435, column 2, paragraph 2 – page 436, column 1, paragraph 2).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate the teachings of Graybill et al. on sequencing approach for microRNA analysis into the method of Wellstein et al. thus arriving at the instantly claimed invention, because sequencing approach for microRNA analysis was one of the three major art-recognized approaches for microRNA analysis (see Graybill et al., page 433, column 2, paragraph 2). In addition, combining prior art elements according to known methods to yield predictable results is considered prima facie obvious (see MPEP 2143.I.A). Given the teachings of the prior art and the level of the ordinary skilled artisan at the effective filing date of the claimed invention, it must be considered, absent evidence to the contrary, that said skilled artisan would have had a reasonable expectation of success in practicing the claimed invention.
Conclusion
17. No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KAIJIANG ZHANG whose telephone number is (571)272-5207. The examiner can normally be reached Monday - Friday, 8:30 am - 5 pm.
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/KAIJIANG ZHANG/Primary Examiner, Art Unit 1684