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 .
Specification
2. The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (see paragraph [00174] of the specification as filed). Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
3. The lengthy specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
Claim Objections
4. Claims 2 and 4 are objected to because of the following informalities:
Claim 2, lines 8-9: “that is the complement a nucleotide sequence of miR-10b-5p” should be changed to “that is the complement to a nucleotide sequence of miR-10b-5p” for more clarity.
Claim 4, line 3: “the nucleotide SEQ ID NO: 3” should be changed to “the nucleotide sequence of SEQ ID NO: 3” for more clarity.
Appropriate correction is required.
Double Patenting
5. 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.
6. Claims 1-2 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2 of U.S. Patent No. 10,577,645 in view of Zhou et al. (Anal. Biochem. 2017, 536:8-15).
Claims 1-2 of U.S. Patent No. 10,577,645 disclose all the steps and elements of the instantly claimed method, except the alternative use of a urine sample wherein the highly expressed miRNAs such as miR-10a-5p fragments and/or miR-10b-5p fragments are to be blocked in (and then depleted from) the population of RNA molecules derived from said urine sample.
However, Zhou et al. teach the use of urine samples for expression analysis, wherein miR-10a (i.e., miR-10a-5p) and miR-10b (i.e., miR-10b-5p) are identified as the most highly expressed noncoding RNAs (ncRNAs) or microRNAs in the urine samples (see Abstract; page 10, column 1, paragraph 6; page 13, column 2, last paragraph; Tables 2-3). Zhou et al. further teach that urine-based biomarkers would be ideal for many studies because of the accessible nature of urine (see page 9, column 1, paragraph 2) and that high-throughput sequencing studies have fueled the search for “novel” ncRNA biomarkers [which may not be highly expressed like miR-10a or miR-10b, or which may be expressed in low levels] from such accessible urine samples (page 12, column 2, paragraph 2).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filling date of the claimed invention to combine the teachings of Zhou et al. with the claimed method of U.S. Patent No. 10,577,645 to arrive at the instantly claimed invention (wherein the most highly expressed microRNAs in a urine sample, such as miR-10a and/or miR-10b, are blocked and then depleted to allow better identification/search for “novel” ncRNA or microRNA biomarkers that are expressed in lower levels), because one of ordinary skill in the art would have been motivated to do so in order to eliminate overly abundant microRNA species (such as miR-10a and/or miR-10b) from urine sample(s) to thereby allow unencumbered, improved analysis/quantification of rarer microRNA species as potential “novel” biomarkers.
Claim Rejections - 35 USC § 102
7. 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.
8. 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.
9. Claims 1-2 and 4-5 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Baraniuk et al. (US 2016/0194716 A1).
Regarding claims 1-2
Baraniuk et al. teach a method comprising the step of blocking miR-10a-5p (e.g., “hsa-miR-10a-5p (SEQ ID NO:6)”) fragments and/or miR-10b-5p (e.g., “hsa-miR-10b-5p (SEQ ID NO:8)”) fragments in a population of RNA molecules derived from human urine (see paragraphs [0008], [0012] and [0019]), wherein the step of blocking the miR-10a-5p fragments and/or miR-10b-5p fragments in the population of RNA molecules comprises: adding miR-10a-5p specific oligonucleotide probes and/or miR-10b-5p specific oligonucleotide probes to a sample containing the population of RNA molecules, wherein each miR-10a-5p specific oligonucleotide probe comprises a nucleotide sequence that is the complement to a nucleotide sequence of miR-10a-5p and each miR-10b-5p specific oligonucleotide probe comprises a nucleotide sequence that is the complement of a nucleotide sequence of miR-10b-5p (see paragraph [0019]); and forming a complex between one or more miR-10a-5p fragments and a miR-10a-5p specific oligonucleotide probe and/or forming a complex between one or more miR-10b-5p fragments and a miR-10b-5p specific oligonucleotide probe to provide a miR-10a-5p and/or miR-10b-5p blocked sample (see paragraph [0019]).
Regarding the recitation “improving global gene expression analysis” in the preamble, it is merely a recitation of an intended use of the claimed method. Since claims 1-2 do not recite any step of “global gene expression analysis” and Baraniuk et al. teach all the steps and elements recited in the body of the claims, there is no manipulative difference between the claimed method and the method of Baraniuk et al.
Regarding claim 4
The method according to Baraniuk et al., wherein the nucleotide sequence of miR-10a-5p (e.g., “hsa-miR-10a-5p (SEQ ID NO:6)”) has 100% identity to the nucleotide sequence of SEQ ID NO: 1 and wherein the nucleotide sequence of miR-10b-5p (e.g., “hsa-miR-10b-5p (SEQ ID NO:8)”) has 100% identity to the nucleotide sequence of SEQ ID NO: 3 (see Sequence Listing below paragraph [0057]).
Regarding claim 5
The method according to Baraniuk et al., wherein the miR-10a-5p specific oligonucleotide probe has at least 90% identity to the nucleotide sequence of SEQ ID NO: 2 and the miR-10b-5p specific oligonucleotide probe has at least 90% identity to the nucleotide sequence of SEQ ID NO: 4 (see paragraph [0019]: “…the provided probes are fully complementary to the sequences of SEQ ID NOs:1-57.”).
Claim Rejections - 35 USC § 103
10. 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.
11. Claims 1-6 are rejected under 35 U.S.C. 103 as being unpatentable over O’Neil et al. (US 2015/0275267 A1) in view of Zhou et al. (Anal. Biochem. 2017, 536:8-15).
Regarding claims 1-2
O’Neil et al. teach, throughout the whole document, a method of improving global gene expression analysis (see paragraphs [0020] and [0075]) for a population of RNA molecules derived from human blood, serum or urine (see paragraph [0091]), the method comprising a step of blocking unwanted RNA species (or RNA species that are not of interest for subsequent analysis) in the population of RNA molecules [and a further step of depleting said unwanted RNA species from the population of RNA molecules] (see Abstract and the claims), wherein the step of blocking unwanted RNA species in the population of RNA molecules comprises: adding unwanted RNA species-specific oligonucleotide probes to a sample containing the population of RNA molecules, wherein each oligonucleotide probe comprises a nucleotide sequence that is the complement to a nucleotide sequence of an unwanted RNA species; and forming a complex between each unwanted RNA species and its corresponding oligonucleotide probe to provide a unwanted RNA species-blocked sample (see Abstract and the claims, as well as paragraphs [0010]-[0035]). While O’Neil et al. teach blocking of unwanted RNA species (or RNA species that are not of interest for subsequent analysis) in a population of RNA molecules derived from human blood, serum or urine [and then depleting said unwanted RNA species from the population of RNA molecules], O’Neil et al. do not specifically disclose blocking/depleting miR-10a-5p fragments and/or miR-10b-5p fragments in/from a population of RNA molecules derived from human urine.
However, Zhou et al. teach expression analysis of RNA molecules derived from human urine, wherein miR-10a (i.e., miR-10a-5p) and miR-10b (i.e., miR-10b-5p) are identified as the most highly expressed noncoding RNAs (ncRNAs) or microRNAs in urine samples (see Abstract; page 10, column 1, paragraph 6; page 13, column 2, last paragraph; Tables 2-3). Zhou et al. further teach that urine-based biomarkers would be ideal for many studies because of the accessible nature of urine (see page 9, column 1, paragraph 2) and that high-throughput sequencing studies have fueled the search for “novel” ncRNA biomarkers [which may not be highly expressed like miR-10a or miR-10b, or which may be expressed in low levels] from such accessible urine samples (page 12, column 2, paragraph 2).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filling date of the claimed invention to combine the teachings of Zhou et al. and O’Neil et al. to arrive at the instantly claimed invention (wherein the most highly expressed microRNAs in a urine sample, such as miR-10a and/or miR-10b, are blocked and then depleted to allow better identification/search for “novel” ncRNA or microRNA biomarkers that are expressed in lower levels), because one of ordinary skill in the art would have been motivated to do so in order to eliminate overly abundant microRNA species (such as miR-10a and/or miR-10b) from urine sample(s) to thereby allow unencumbered, improved analysis/quantification of rarer microRNA species as potential “novel” biomarkers. 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 application’s effective filling date, 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.
Regarding claim 3
The method according to O’Neil et al. in view of Zhou et al., wherein the 5’-end, the 3’-end or both ends of each miR-10a-5p specific oligonucleotide probe and/or miR-10b-5p specific oligonucleotide probe is modified to prevent ligation and wherein the modification is a 5’ biotin modification, a 3’ biotin modification, or a combination thereof (see O’Neil et al., paragraphs [0006] and [0059]; Figure 1).
Regarding claims 4-5
Since miR-10a-5p (i.e., miR-10a) and miR-10b-5p (i.e., miR-10b) were known microRNAs and their sequences were known before the effective filling date of the claimed invention, the nucleotide sequences of miR-10a-5p (i.e., miR-10a) and miR-10b-5p (i.e., miR-10b) would be the same as (i.e., have 100% identity to) the nucleotide sequence of SEQ ID NO: 1 and the nucleotide sequence of SEQ ID NO: 3 respectively. Since O’Neal et al. teach the use of oligonucleotide probe having a nucleotide sequence that is the complement to a nucleotide sequence of the RNA species to be blocked/depleted (see rejection of claims 1-2 as discussed above), it would be obvious to use miR-10a-5p specific oligonucleotide probe having 100% identity to the nucleotide sequence of SEQ ID NO: 2 and miR-10b-5p specific oligonucleotide probe having 100% identity to the nucleotide sequence of SEQ ID NO: 4.
Regarding claim 6
The method according to O’Neil et al. in view of Zhou et al., wherein the global gene expression analysis is next generation sequencing and wherein the method further comprises the steps of: preparing a library using the miR-10a-5p and/or miR-10b-5p blocked sample; and sequencing the library (see O’Neil et al., Abstract; paragraphs [0003]-[0010], [0026], [0045], [0075], [0100], [0105]-[0106] and [0161]).
Conclusion
12. 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