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 Group I (encompassing claims 1-9, as well as newly added claims 23-33 that depend from claim 1) in the reply filed on 5/29/2026 is acknowledged.
3. Since applicant has canceled claims 10-22 in the non-elected Groups II-III, claims 1-9 and 23-33 are currently pending and under examination.
Double Patenting
4. 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.
5. Claims 1-9, 23-25 and 29-33 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 of U.S. Patent No. 11,525,134. Although the claims at issue are not identical, they are not patentably distinct from each other because claims 1-21 of U.S. Patent No. 11,525,134 teach or render obvious all the features as recited in instant claims 1-9, 23-25 and 29-33.
Specifically, claims 1, 8 and 14 of U.S. Patent No. 11,525,134 teach all the steps and elements required by instant claim 1. In addition, the other features as recited in dependent claims 2-9, 23-25 and 29-33 are also taught or rendered obvious by claims 1-21 of U.S. Patent No. 11,525,134.
Claim Rejections - 35 USC § 112
6. 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.
7. Claim 28 is 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a new matter rejection.
In the set of claims filed on 5/29/2026, newly added claim 28 (which depends from claim 1) recites “wherein the detecting comprises: (i) contacting the cell-free nucleic acids with one or more methylation-sensitive restriction enzymes, thereby digesting unmethylated copies of the at least one target nucleic acid sequence while preserving methylated copies thereof; and (ii) amplifying and detecting the preserved methylated copies by quantitative polymerase chain reaction (PCR)”. However, no support for such newly added features could be found in the disclosure as filed.
Applicants submit that “[t]he newly added claims are fully supported by pending claims and throughout the application as originally filed, U.S. Patent Application No. 17/938,284, now U.S. Patent Publication No. 2023/0051179 at, for example, paragraphs [0044], [0050], [0064], [0067], [0120], [0128], [0132], [0139], [0141], [0181]-[0182], [0184]-[0185], [0266], [0190], [0335], and [0373]” (see page 4 of applicant's response filed on 5/29/2026).
The original disclosure, in particular the paragraphs corresponding to paragraphs [0044], [0050], [0064], [0067], [0120], [0128], [0132], [0139], [0141], [0181]-[0182], [0184]-[0185], [0266], [0190], [0335], and [0373] of U.S. Patent Publication No. 2023/0051179, has been thoroughly reviewed, but no support for the newly added features as recited in claim 28 could be found.
Applicants are reminded that it is their burden to show where the specification supports any amendments to the disclosure. See MPEP 714.02, paragraph 5, last sentence and also MPEP 2163.06.I.
MPEP 2163.06 notes “If new matter is added to the claims, the examiner should reject the claims under 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph - written description requirement. In re Rasmussen, 650 F.2d 1212, 211 USPQ 323 (CCPA 1981).” MPEP 2163.02 teaches that “Whenever the issue arises, the fundamental factual inquiry is whether a claim defines an invention that is clearly conveyed to those skilled in the art at the time the application was filed...If a claim is amended to include subject matter, limitations, or terminology not present in the application as filed, involving a departure from, addition to, or deletion from the disclosure of the application as filed, the examiner should conclude that the claimed subject matter is not described in that application.” MPEP 2163.06 further notes: When an amendment is filed in reply to an objection or rejection based on 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph, a study of the entire application is often necessary to determine whether or not “new matter” is involved. Applicants should therefore specifically point out the support for any amendments made to the disclosure.
8. 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.
9. Claim 8 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 8, dependent from claim 1, recites “wherein the plasma or serum sample is generated upon or after obtaining the capillary blood sample from the subject” (emphasis provided). Since the plasma or serum sample could NOT be generated before the capillary blood sample is obtained from the subject and could only be generated upon or after the capillary blood sample is obtained from the subject (i.e., there is no other alternative to the two options recited in claim 8), claim 8 is of improper dependent form for failing to further limit the subject matter of the claim (i.e., claim 1) 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.
Claim Rejections - 35 USC § 102
10. 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.
11. 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
12. Claims 1-9, 23-27 and 29-33 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Yeh (WO 2017/027835 A1).
Regarding claim 1
Yeh teaches, throughout the whole document, a method comprising: (a) obtaining or providing capillary blood (e.g., finger-prick blood) comprising cell-free nucleic acids obtained from a subject (see page 3, paragraph 1; page 8, paragraph 4); (b) separating plasma or serum (via centrifugation) from the capillary blood or a portion thereof, thereby generating a plasma or serum sample (see page 24, paragraph 1; page 56, paragraph 6); (c) extracting cell-free nucleic acids from the plasma or serum sample (see page 56, paragraph 6; Example 6 at pages 68-69); and (d) detecting an overrepresentation, an underrepresentation, or a normal representation of at least one target nucleic acid sequence in the cell-free nucleic acids (see page 16, paragraph 2; page 48, paragraph 1; Example 6 at pages 68-69).
Regarding claims 2-4
The method according to Yeh, wherein the extracting of (c) comprises binding the cell-free nucleic acids to a solid support (e.g., silica-based membrane spin-column) from QIAamp Circulating Nucleic Acid kit (see page 56, paragraph 6), wherein using said kit would involve a step of eluting the cell-free nucleic acids from the solid support.
Regarding claim 5
The method according to Yeh, further comprising, purifying the cell-free nucleic acids after ligation with corresponding barcoded adapters (see page 61, last paragraph: “…followed by ligation with corresponding barcoded adapters and purified using Ampure Beads.”).
Regarding claim 6
The method according to Yeh, wherein the separating of (b) comprises centrifuging the capillary blood (see page 24, paragraph 1; page 56, paragraph 6).
Regarding claim 7
The method according to Yeh, wherein the detecting of (d) comprises sequencing the at least one target sequence in the cell-free nucleic acids (see page 16, paragraph 1; page 17, paragraph 3; page 18, paragraph 4; page 20, paragraph 3; page 21, paragraph 4; page 26, paragraph 3; page 30, paragraph 3; page 47, last paragraph; paragraph bridging pages 61-62).
Regarding claim 8
The method according to Yeh, wherein the plasma or serum sample is generated (via centrifugation) upon or after obtaining the capillary blood sample from the subject (see page 24, paragraph 1; page 56, paragraph 6).
Regarding claim 9
The method according to Yeh, wherein a total volume of the capillary blood is from about 5 µL to about 1 mL (see page 8, paragraphs 3-4).
Regarding claims 23-25
The method according to Yeh, further comprising enriching the cell-free nucleic acids thereby generating enriched cell-free nucleic acids, wherein the enriching comprises enriching the at least one target nucleic acid sequence in the cell-free nucleic acids, and wherein the enriching comprises removing white blood cells, cellular nucleic acids, or both, from the capillary blood (see paragraph bridging pages 2-3; page 56, paragraph 6; Example 6 at pages 68-69).
Regarding claim 26
The method according to Yeh, wherein the at least one target nucleic acid sequence comprises a tissue-specific methylation pattern (see page 16, paragraph 2; page 17, paragraph 4; page 20, paragraph 4; page 21, paragraph 5; page 48, paragraph 1).
Regarding claim 27
The method according to Yeh, wherein the detecting comprises detecting an epigenetic modification of the at least one target nucleic acid sequence (see paragraph bridging pages 26-27; page 48, paragraph 1).
Regarding claim 29
The method according to Yeh, wherein the subject has, is suspected of having, or is at risk of developing cancer, and wherein the at least one target nucleic acid sequence comprises cell-free tumor nucleic acids (see page 33, paragraph 2; page 49, paragraph 3; page 62, paragraph 2).
Regarding claim 30
The method according to Yeh, wherein the cancer comprises lung cancer, bladder cancer, or any combination thereof (see page 80, the 1st full paragraph; page 86, paragraph 3).
Regarding claim 31
The method according to Yeh, wherein the cancer comprises a metastatic cancer (see page 86, paragraph 3; page 87, paragraph 1).
Regarding claim 32
The method according to Yeh, wherein the cancer is at stage 0 or stage 1 (e.g., early stage, such as stage 0 or stage 1, of cancer detected during “early detection”) (see page 27, paragraph 4).
Regarding claim 33
The method according to Yeh, further comprising determining a treatment response to the cancer from the overrepresentation, the underrepresentation, or the normal representation of the at least one target nucleic acid sequence in the cell-free nucleic acids (see page 19, paragraph 2 – page 20, paragraph 1).
Claim Rejections - 35 USC § 103
13. 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.
14. 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.
15. Claims 1-9, 23-25 and 29-33 are rejected under 35 U.S.C. 103 as being unpatentable over Srinivasan et al. (WO 2014/145078 A1) in view of Jackson et al. (US 2017/0067803 A1).
Regarding claim 1
Srinivasan et al. teach, throughout the whole document, a method comprising: (a) obtaining or providing a blood sample comprising cell-free nucleic acids obtained from a subject (see Abstract; page 2, line 26 – page 3, line 6; page 34, lines 1-28; Figures 1A and 2A); (b) separating plasma or serum from the blood sample or a portion thereof, thereby generating a plasma or serum sample (see page 2, line 26 – page 3, line 6; page 34, lines 1-28; Figures 1A and 2A); (c) extracting cell-free nucleic acids from the plasma or serum sample (see page 2, line 26 – page 3, line 11; page 34, lines 1-28; page 73, line 18 – page 77, line 17; Figures 1A and 2A); and (d) detecting an overrepresentation, an underrepresentation, or a normal representation of the at least one target nucleic acid sequence in the cell-free nucleic acids (see Abstract; page 2, lines 22-24; paragraph bridging pages 59-60; page 53, lines 12-15; page 85, lines 19-25). Srinivasan et al. do not specifically disclose the use of capillary blood as the blood sample.
However, Jackson et al. teach the use of capillary blood as the blood sample, as well as a sample acquisition device for collecting capillary blood (see paragraphs [0042]-[0046] and Figure 1A). According to Jackson et al., the capillary blood sample collecting device is configured for “pain-free” and “efficient sample transfer” and can be designed to “minimize physical pain or discomfort to the user” (see paragraph [0042]).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the present application to use the capillary blood sample collecting device, as taught by Jackson et al., to collect the blood sample in the method of Srinivasan et al. thus arriving at the instantly claimed invention, because applying a known technique (e.g., using the capillary blood sample collecting device as taught by Jackson et al. to collect a blood sample) to a known method ready for improvement (e.g., using the capillary blood sample collecting device as taught by Jackson et al. to collect the blood sample used in the method of Srinivasan et al. would improve the blood sample collection because the capillary blood sample collecting device is configured for “pain-free” and “efficient sample transfer” and can be designed to “minimize physical pain or discomfort to the user”) to yield predictable results is considered prima facie obvious (see MPEP 2143.I.D). Given the teachings of the prior art and the level of the ordinary skilled artisan at the time of the application’s effective filing 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 2
The method according to Srinivasan et al. in view of Jackson et al., wherein the extracting of (c) comprises binding the cell-free nucleic acids to a solid support (see Srinivasan et al., page 20, lines 19-22; page 22, lines 6-9).
Regarding claim 3
The method according to Srinivasan et al. in view of Jackson et al., wherein the solid support is selected from the group consisting of: a bead, a nanoparticle, a magnetic particle, a chip, a microchip, a fibrous strip, a polymer strip, a membrane, a matrix (e.g., support matrix), a column, a plate, and any combination thereof (see Srinivasan et al., page 20, lines 19-22; page 22, lines 6-9).
Regarding claim 4
The method according to Srinivasan et al. in view of Jackson et al., further comprising, eluting the cell-free nucleic acids from the solid support (see Srinivasan et al., page 24, lines 25-26; page 26, lines 13-15; page 74, lines 1-9).
Regarding claim 5
The method according to Srinivasan et al. in view of Jackson et al., further comprising, purifying the cell-free nucleic acids (see Srinivasan et al., page 20, lines 19-22; page 22, lines 6-9).
Regarding claim 6
The method according to Srinivasan et al. in view of Jackson et al., wherein the separating of (b) comprises centrifuging the capillary blood, filtering the capillary blood, or both (see Srinivasan et al., page 2, line 26 – page 3, line 9; Figures 1A and 2A).
Regarding claim 7
The method according to Srinivasan et al. in view of Jackson et al., wherein the detecting of (d) comprises sequencing the at least one target sequence in the cell-free nucleic acids (see Srinivasan et al., page 2, lines 26-31; Figures 1A and 2A).
Regarding claim 8
The method according to Srinivasan et al. in view of Jackson et al., wherein the plasma or serum sample is generated upon or after obtaining the capillary blood sample from the subject (see Srinivasan et al., page 2, line 26 – page 3, line 11; page 34, lines 1-28; Figures 1A and 2A).
Regarding claim 9
The method according to Srinivasan et al. in view of Jackson et al., wherein a total volume of the capillary blood is from about 5 µL to about 1 mL (see Jackson et al., paragraph [0043]).
Regarding claims 23-24
The method according to Srinivasan et al. in view of Jackson et al., further comprising enriching the cell-free nucleic acids thereby generating enriched cell-free nucleic acids, wherein the enriching comprises enriching the at least one target nucleic acid sequence in the cell-free nucleic acids (see Srinivasan et al., page 18, lines 22-25; page 51, paragraph 2).
Regarding claim 25
The method according to Srinivasan et al. in view of Jackson et al., wherein the enriching comprises removing white blood cells, cellular nucleic acids, or both, from the capillary blood (see Srinivasan et al., page 10, lines 3-11; page 21, lines 6-9; page 31, lines 16-30).
Regarding claim 29
The method according to Srinivasan et al. in view of Jackson et al., wherein the subject has, is suspected of having, or is at risk of developing cancer, and wherein the at least one target nucleic acid sequence comprises cell-free tumor nucleic acids (see Srinivasan et al., Abstract; page 4, lines 5-10; page 5, lines 15-18).
Regarding claim 30
The method according to Srinivasan et al. in view of Jackson et al., wherein the cancer comprises lung cancer, bladder cancer, or any combination thereof (see Srinivasan et al., page 63, lines 8-12).
Regarding claim 31
The method according to Srinivasan et al. in view of Jackson et al., wherein the cancer comprises a metastatic cancer (see Srinivasan et al., page 19, last paragraph; paragraph bridging pages 62-63).
Regarding claim 32
The method according to Srinivasan et al. in view of Jackson et al., wherein the cancer is at stage 0 or stage 1 (see Srinivasan et al., page 33, paragraph 2).
Regarding claim 33
The method according to Srinivasan et al. in view of Jackson et al., further comprising determining a treatment response to the cancer from the overrepresentation, the underrepresentation, or the normal representation of the at least one target nucleic acid sequence in the cell-free nucleic acids (see Srinivasan et al., page 33, paragraph 2; page 57, paragraph 3; page 62, paragraph 1).
Conclusion
16. 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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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Heather Calamita can be reached on 571-272-2876. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KAIJIANG ZHANG/Primary Examiner, Art Unit 1684
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