DETAILED ACTION
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 .
Response to Amendment
The amendment filed March 17th, 2026 is acknowledged. Regarding the Office Action mailed December 17th, 2025:
The objections to the drawings are withdrawn in view of the amendments.
The objections to the specification are withdrawn in view of the amendments.
The rejections set forth under 35 U.S.C. 112(b) are withdrawn in view of the amendments.
Maintained, modified, or new rejections are set forth below, as necessitated by the amendments. Responses to arguments, if necessary, follow their respective rejection sections.
Claim Summary
Claims 1, 4, 17, 18, and 28 have been amended. Claims 20-27 and 29-77 have been canceled. Claims 1-19 and 28 are pending. Claims 1-19 and 28 are under examination and discussed in this Office action.
Claim Rejections - 35 USC § 112(b) - New - Necessitated by Amendment
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 1-19 and 28 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.
Claims 1, 4-5, 8-11, 15-16, 18, and 28 all recite the limitation "the target nucleic acid". There is insufficient antecedent basis for this limitation in the claims. In claims 1, 18, and 28, there is “a fragmented target nucleic acid” introduced. Further recitations in claims 1, 18, and 28, as well as the dependent claims cited above, do not recite “the fragmented target nucleic acid”, but instead “the target nucleic acid”, which lacks antecedent basis. Therefore, the claims are found indefinite. Claims 2-3, 6-7, 12-14, 17, and 19 are also rejected here for their dependence on the above rejected independent claims and not further clarifying the identified issue.
Claim Rejections - 35 USC § 103 - Modified - Necessitated by Amendment
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-2, 4-18, and 28 are rejected under 35 U.S.C. 103 as being unpatentable over Zhuang (US20190264270A1; cited on the IDS filed August 22nd, 2023), in view of Qiagen (Successful biomarker profiling from FFPE samples, Qiagen, August 2020, 1-12).
Regarding instant claim 1, Zhuang teaches a method of anchoring target nucleic acid within a matrix and clearing non-target cellular components comprising: a. contacting a tissue sample with an anchoring agent, wherein the anchoring agent can either form a covalent bond with the target nucleic acid or comprises an oligonucleotide that hybridizes with the target nucleic acid (Page 2, paragraph [0027]; Page 4, paragraphs [0043]-[0044]) ; b. embedding the sample in a polymer matrix wherein the anchoring agent forms a covalent bond with the polymer matrix (Page 3, paragraph [0039]; Page 4, paragraph [0042] and paragraph [0044]; Page 4, paragraph [0047]); and, c. clearing the non-target cellular components from the polymer matrix wherein the target nucleic acid remains anchored in the polymer matrix to form a matrix anchored target nucleic acid sample (Page 4, paragraph [0048]).
Zhuang does not expressly teach wherein at least two anchoring agents are used together to anchor the target nucleic acid to the polymer matrix. However, as indicated above, Zhuang teaches both an anchoring agent that forms a covalent bond with the target nucleic acid and an anchoring agent that comprises an oligonucleotide that hybridizes with the target nucleic acid (Page 4, paragraphs [0043]-[0044]). Both of these options are taught as being able to form a covalent bond with a polymer matrix (Page 4, paragraph [0042] and paragraph [0044]). In addition, Zhuang teaches that a plurality of anchor probes may be used (Page 2, paragraph [0027]), indicating many anchoring agents are present to anchor target nucleic acids to the gel. Therefore, it would be obvious that at least two anchoring agents, both a first anchoring agent that forms a covalent bond with the target and a second anchoring agent comprising an oligonucleotide probes that hybridize with the target, can be used together to anchor a target nucleic acid. This is further supported by the idea that combining equivalents known for the same purpose is considered obvious. The courts have stated, “[i]t is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). See also In re Crockett, 279 F.2d 274, 126 USPQ 186 (CCPA 1960), Ex parte Quadranti, 25 USPQ2d 1071 (Bd. Pat. App. & Inter. 1992), and In re Couvaras, 70 F.4th 1374, 1378-79, 2023 USPQ2d 697 (Fed. Cir. 2023) (see MPEP 2144.06)
Zhuang teaches that target nucleic acids may be DNA, RNA, or other nucleic acids present in a sample (Page 3, paragraph [0032]). Zhuang teaches that a sample may be a tissue sample (Page 2, paragraph [0027]). Zhuang also teaches that a tissue sample may be fixed prior to probe introduction to preserve positions of nucleic acids in the sample (Page 5, paragraph [0053]). However, Zhuang does not teach on fragmented nucleic acid in a tissue sample.
Qiagen, in a reasonably pertinent field, teaches on FFPE tissue sections having nucleic acid fragmentation that results from the fixation process (Page 2), therefore teaching on fragmented nucleic acid in a tissue sample.
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the target nucleic acid and tissue sample of Zhuang with the fragmented nucleic acid and FFPE tissue sample of Qiagen. Since Qiagen teaches on FFPE tissue samples for downstream analysis, which is reasonably pertinent to the methods of Zhuang, one of ordinary skill in the art would combine the two teachings with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to make this modification because it amounts to substitution of one known element for another to obtain predictable results (see MPEP 2141(III)). Zhuang teaches on target nucleic acids being any of DNA, RNA, or other nucleic acids and fixing tissues samples before applications, and the FFPE tissue of Qiagen is a fixed tissue with fragmented nucleic acids. Furthermore, one of ordinary skill in the art would have been motivated to make this modification because FFPE tissue sections are a valuable and extensive source of material for biomedical research (Qiagen, Page 2).
Regarding instant claim 2, Zhuang, in view of Qiagen, teaches the method of claim 1, wherein the first anchoring agent is an alkylating agent (Page 4, paragraph [0044]; see 103 analysis regarding first and second anchoring agents in claim 1).
Regarding instant claim 4, Zhuang, in view of Qiagen, teaches the method of claim 1. Zhuang further teaches wherein the second anchoring agent comprises alternating dT and locked dT portions that hybridize with the target nucleic acid (Page 4, paragraph [0043]; see 103 analysis regarding first and second anchoring agents in claim 1).
Regarding instant claim 5, Zhuang, in view of Qiagen, teaches the method of claim 1. Zhuang further teaches wherein the second anchoring agent comprises a poly-dT portion that hybridizes to the target nucleic acid (Page 4, paragraph [0043]; see 103 analysis regarding first and second anchoring agents in claim 1).
Regarding instant claim 6, Zhuang, in view of Qiagen, teaches the method of claim 1. Zhuang further teaches wherein the second anchoring agent comprises an acrydite moiety that covalently binds the polymer matrix (Page 4, paragraphs [0042]-[0043]; see 103 analysis regarding first and second anchoring agents in claim 1). Zhuang does not specifically teach that the first anchoring agent comprises an acrydite moiety. However, the above citation indicates that an acrydite moiety can polymerize and become incorporated into a polyacrylamide polymer. Zhuang later teaches that the first anchoring agent, which covalently binds with the target, may have a chemical moiety that can be incorporated into a polyacrylamide polymer as in polymerizes (Page 4, paragraph [0044]; see 103 analysis regarding first and second anchoring agents in claim 1). Therefore, it would be obvious that the chemical moiety for this purpose could be acrydite.
Regarding instant claim 7, Zhuang, in view of Qiagen, teaches the method of claim 1. Zhuang teaches wherein the first anchoring agent that is an alkylating agent has a chemical moiety that can be incorporated into a polyacrylamide polymer as it polymerizes (Page 4, paragraph [0044]; see 103 analysis for claim 1 regarding having a first and second anchoring agent). Zhuang does not specifically teach that the first anchoring agent is derivatized with an acrydite moiety. Zhuang earlier teaches that an anchoring probe can comprise an acrydite moiety that can polymerize and become incorporated into a polyacrylamide polymer (Page 4, paragraphs [0042]-[0043]). Therefore, it would be obvious that the chemical moiety for this purpose could be acrydite. wherein the first anchoring agent is an alkylating agent derivatized with an acrydite moiety.
Regarding instant claim 8, Zhuang, in view of Qiagen, teaches the method of claim 1. Zhuang further teaches wherein the second anchoring agent comprises a poly-dT portion that hybridizes to the target nucleic acid and an acrydite moiety that covalently binds the polymer matrix (Page 4, paragraph [0043]; see 103 analysis regarding first and second anchoring agents in claim 1).
Regarding instant claim 9, Zhuang, in view of Qiagen, teaches the method of claim 1. Zhuang further teaches wherein the target nucleic acid is RNA (Page 2, paragraph [0027]-[0028]).
Regarding instant claim 10, Zhuang, in view of Qiagen, teaches the method of claim 1. Zhuang further teaches wherein the target nucleic acid is DNA (Page 2, paragraph [0027]-[0028]).
Regarding instant claim 11, Zhuang, in view of Qiagen, teaches the method of claim 1. Zhuang further teaches the method further comprising contacting the anchored target nucleic acid sample with one or more primary oligonucleotide probes that hybridize to the target nucleic acids (Page 5, paragraph [0055]; Page 14, paragraph [0113]: where “encoding probe” is equivalent to a primary probe; Page 25, Claims 16 and 18, indicating that there is an option where the order of the method is the target is anchored, the non-targets are cleared, and then the sample is exposed to a plurality of probes).
Regarding instant claim 12, Zhuang, in view of Qiagen, teaches the method of claim 11. Zhuang further teaches wherein the primary oligonucleotide probes are multiplexed error robust fluorescence in situ hybridization (MERFISH) probes (Page 5, paragraph [0051]; Page 5, paragraph [0055]; Page 14, paragraph [0113]: where “encoding probe” is equivalent to a primary probe).
Regarding instant claim 13, Zhuang, in view of Qiagen, teaches the method of claim 11. Zhuang further teaches wherein the one or more primary oligonucleotide probes comprise a first portion comprising a target sequence and a second portion comprising one or more read sequences (Page 6, paragraph [0059]; Page 6, paragraph [0063]; Page 14, paragraph [0113]: where “encoding probe” is equivalent to a primary probe and a “readout sequence” is equivalent to a read sequence as taught in paragraph [0059]).
Regarding instant claim 14, Zhuang, in view of Qiagen, teaches the method of claim 13. Zhuang further teaches the method further comprising determining read sequences based on contacting the one or more primary oligonucleotide probes with a plurality of secondary nucleic acid probes comprising a recognition sequence that hybridizes to the read sequence of the primary nucleic acid probe (Page 5, paragraph [0055]; Page 7, paragraph [0070]; Page 14, paragraph [0113]: where “encoding probe” is equivalent to a primary probe, “readout probe” is equivalent to a secondary probe, and “readout sequence” is equivalent to read sequence).
Regarding instant claim 15, Zhuang, in view of Qiagen, teaches the method of claim 1. Zhuang further teaches the method further comprising imaging using multiplexed fluorescence in situ hybridization comprising contacting the anchored target nucleic acid sample with one or more primary oligonucleotide probes that hybridize to the target nucleic acids (Page 5, paragraph [0051]; Page 5, paragraph [0055]; Page 14, paragraph [0113]: where “encoding probe” is equivalent to a primary probe) and comprising one or more sequential steps of adding a plurality of secondary nucleic acid probes comprising a label moiety (Page 7, paragraph [0070]: secondary probes hybridize to read sequences of primary probes; Page 14, paragraph [0113]: where “readout probe” is equivalent to a secondary probe, and readout probes with fluorescent dye bind to readout sequences (equivalent to read sequences) in a sequential process of cleaving and staining).
Regarding instant claim 16, Zhuang, in view of Qiagen, teaches the method of claim 1. Zhuang further teaches the method further comprising imaging using multiplexed error robust fluorescence in situ hybridization (MERFISH) probes comprising contacting the anchored target nucleic acid sample with one or more MERFISH probes that hybridize to the target nucleic acids (Page 5, paragraph [0051]; Page 5, paragraph [0055]).
Regarding instant claim 17, Zhuang, in view of Qiagen, teaches the method of claim 13. Zhuang further teaches the method further comprising imaging using multiple rounds of fluorescence in situ hybridization wherein, in each round, one or more different secondary nucleic acid probes, each conjugated to a spectrally distinct fluorescent label are used to read out multiple read sequences simultaneously (Page 14, paragraph [0113]: where “readout probes” are equivalent to secondary probes, and they can be conjugated to a spectrally distinct fluorescent dye).
Regarding instant claim 18, Zhuang teaches a method of anchoring target nucleic acid within a matrix and clearing non-target cellular components comprising: a. contacting a tissue sample with an anchoring agent, wherein the anchoring agent is either an alkylating agent that forms a covalent bond with the target nucleic acid or comprises a polyT sequence that is complementary and hybridizes to the target RNA (Page 2, paragraph [0027]; Page 4, paragraphs [0043]-[0044]) and wherein an oligonucleotide with a polyT sequence comprises an acrydite moiety that covalently binds the polymer matrix (Page 4, paragraphs [0042]-[0043]) and an alkylating agent that forms a covalent bond can comprise a chemical moiety that can be incorporated into a polyacrylamide polymer as it polymerizes (Page 4, paragraph [0044]); b. embedding the sample in a polymer matrix wherein the anchoring agent forms a covalent bond with the polymer matrix (Page 3, paragraph [0039]; Page 4, paragraph [0042] and paragraph [0044]; Page 4, paragraph [0047]); and, c. clearing the non-target cellular components from the polymer matrix wherein the target nucleic acid remains anchored in the polymer matrix to form a matrix anchored target nucleic acid sample (Page 4, paragraph [0048]). Zhuang further teaches that the target nucleic acid is RNA (Page 2, paragraph [0027]-[0028]).
Zhuang does not expressly teach wherein at least two anchoring agents are used together to anchor the target nucleic acid to the polymer matrix. However, as indicated above, Zhuang teaches both an anchoring agent that comprises an alkylating agent that forms a covalent bond with the target nucleic acid and an anchoring agent that comprises a polyT sequence that hybridizes with the target nucleic acid (Page 4, paragraphs [0043]-[0044]). Both of these options are taught as being able to form a covalent bond with a polymer matrix (Page 4, paragraph [0042] and paragraph [0044]). In addition, Zhuang teaches that a plurality of anchor probes may be used (Page 2, paragraph [0027]), indicating many anchoring agents are present to anchor target nucleic acids to the gel. Therefore, it would be obvious that at least two anchoring agents, both a first anchoring agent comprising an alkylating agent that forms a covalent bond with the target and a second anchoring agent comprising a polyT sequence that is complementary and hybridizes with the target, can be used together to anchor a target nucleic acid. This is further supported by the idea that combining equivalents known for the same purpose is considered obvious. As noted above, the courts have stated, “[i]t is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.”
Zhuang teaches that target nucleic acids may be DNA, RNA, or other nucleic acids present in a sample (Page 3, paragraph [0032]). Zhuang teaches that a sample may be a tissue sample (Page 2, paragraph [0027]). Zhuang also teaches that a tissue sample may be fixed prior to probe introduction to preserve positions of nucleic acids in the sample (Page 5, paragraph [0053]). However, Zhuang does not teach on fragmented nucleic acid in a tissue sample.
Qiagen, in a reasonably pertinent field, teaches on FFPE tissue sections having nucleic acid fragmentation that results from the fixation process (Page 2), therefore teaching on fragmented RNA in a tissue sample.
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the target nucleic acid and tissue sample of Zhuang with the fragmented RNA and FFPE tissue sample of Qiagen. Since Qiagen teaches on FFPE tissue samples for downstream analysis, which is reasonably pertinent to the methods of Zhuang, one of ordinary skill in the art would combine the two teachings with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to make this modification because it amounts to substitution of one known element for another to obtain predictable results (see MPEP 2141(III)). Zhuang teaches on target nucleic acids being any of DNA, RNA, or other nucleic acids and fixing tissues samples before applications, and the FFPE tissue of Qiagen is a fixed tissue with fragmented nucleic acids. Furthermore, one of ordinary skill in the art would have been motivated to make this modification because FFPE tissue sections are a valuable and extensive source of material for biomedical research (Qiagen, Page 2).
Regarding instant claim 28, Zhuang teaches a method of anchoring target nucleic acid within a matrix and clearing non-target cellular components comprising: a. contacting a tissue sample with an anchoring agent, wherein the anchoring agent can either form a covalent bond with the target nucleic acid or comprises an oligonucleotide that hybridizes with the target nucleic acid (Page 2, paragraph [0027]; Page 4, paragraphs [0043]-[0044]); b. embedding the sample in a polymer matrix wherein the anchoring agent forms a covalent bond with the polymer matrix (Page 3, paragraph [0039]; Page 4, paragraph [0042] and paragraph [0044]; Page 4, paragraph [0047]); c. clearing the non-target cellular components from the polymer matrix wherein the target nucleic acid remains anchored in the polymer matrix to form a matrix anchored target nucleic acid sample (Page 4, paragraph [0048]); and, d. contacting the anchored target nucleic acid sample with one or more primary oligonucleotide probes that hybridize to the target nucleic acids (Page 5, paragraph [0055]; Page 14, paragraph [0113]: where “encoding probe” is equivalent to a primary probe; Page 25, Claims 16 and 18, indicating that there is an option where the order of the method is the target is anchored, the non-targets are cleared, and then the sample is exposed to a plurality of probes) and a plurality of secondary nucleic acid probes comprising a fluorescent label and a recognition sequence that hybridizes to a sequence of the primary nucleic acid probe (Page 7, paragraph [0070]: secondary probes hybridize to read sequences of primary probes; Page 14, paragraph [0113]: where “readout probe” is equivalent to a secondary probe, and readout probes with fluorescent dye bind to readout sequences (equivalent to read sequences) in a sequential process of cleaving and staining) and imaging the target nucleic acids (Page 14, paragraph [0113]).
Zhuang does not expressly teach wherein at least two anchoring agents are used together to anchor the target nucleic acid to the polymer matrix. However, as indicated above, Zhuang teaches both an anchoring agent that forms a covalent bond with the target nucleic acid and an anchoring agent that comprises an oligonucleotide that hybridizes with the target nucleic acid (Page 4, paragraphs [0043]-[0044]). Both of these options are taught as being able to form a covalent bond with a polymer matrix (Page 4, paragraph [0042] and paragraph [0044]). In addition, Zhuang teaches that a plurality of anchor probes may be used (Page 2, paragraph [0027]), indicating many anchoring agents are present to anchor target nucleic acids to the gel. Therefore, it would be obvious that at least two anchoring agents, both a first anchoring agent that forms a covalent bond with the target and a second anchoring agent comprising an oligonucleotide probes that hybridize with the target, can be used together to anchor a target nucleic acid. This is further supported by the idea that combining equivalents known for the same purpose is considered obvious. As noted above, the courts have stated, “[i]t is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art."
Zhuang teaches that target nucleic acids may be DNA, RNA, or other nucleic acids present in a sample (Page 3, paragraph [0032]). Zhuang teaches that a sample may be a tissue sample (Page 2, paragraph [0027]). Zhuang also teaches that a tissue sample may be fixed prior to probe introduction to preserve positions of nucleic acids in the sample (Page 5, paragraph [0053]). However, Zhuang does not teach on fragmented nucleic acid in a tissue sample.
Qiagen, in a reasonably pertinent field, teaches on FFPE tissue sections having nucleic acid fragmentation that results from the fixation process (Page 2), therefore teaching on fragmented nucleic acid in a tissue sample.
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the target nucleic acid and tissue sample of Zhuang with the fragmented nucleic acid and FFPE tissue sample of Qiagen. Since Qiagen teaches on FFPE tissue samples for downstream analysis, which is reasonably pertinent to the methods of Zhuang, one of ordinary skill in the art would combine the two teachings with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to make this modification because it amounts to substitution of one known element for another to obtain predictable results (see MPEP 2141(III)). Zhuang teaches on target nucleic acids being any of DNA, RNA, or other nucleic acids and fixing tissues samples before applications, and the FFPE tissue of Qiagen is a fixed tissue with fragmented nucleic acids. Furthermore, one of ordinary skill in the art would have been motivated to make this modification because FFPE tissue sections are a valuable and extensive source of material for biomedical research (Qiagen, Page 2).
Claims 3 and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Zhuang (US20190264270A1) and Qiagen (Successful biomarker profiling from FFPE samples, Qiagen, August 2020, 1-12), as applied to claims 1-2, 4-18, and 28, and further in view of Gpatindia (BUSULFAN Synthesis, SAR, MCQ, Chemical Structure and Therapeutic Uses [online]. Gpatindia, [2019] [retrieved on December 10th, 2025]. Retrieved from: https://gpatindia.com/busulfan-synthesis-sar-mcq-and-chemical-structure/; previously cited).
Regarding instant claim 3, Zhuang, in view of Qiagen, teaches the method of claim 2.
Zhuang does not teach wherein the alkylating agent is selected from the group consisting of Altretamine, Bendamustine, Busulfan, Carboplatin, Carmustine, Chlorambucil, Cisplatin, Cyclophosphamide, Dacarbazine, Ifosfamide, Lomustine, Mechlorethamine, Melphalan, Oxaliplatin, Temozolomide, Thiotepa and Trabectedin.
Gpatindia, in a reasonably pertinent field, teaches wherein Busulfan is an alkylating agent (Page 2, Classification).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the alkylating agent of Zhuang with the specific alkylating agent of Gpatindia. Since Gpatindia teaches that Busulfan is an alkylating agent, which is reasonably pertinent to the alkylating agent of Zhuang, one of ordinary skill in the art would combine the two teachings with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to make this combine these references given the knowledge that Busulfan is an alkylating agent (Gpatindia, Page 2, Classification).
Regarding instant claim 19, Zhuang, in view of Qiagen, teaches the method of claim 18.
Zhuang does not teach wherein the alkylating agent is selected from the group consisting of Altretamine, Bendamustine, Busulfan, Carboplatin, Carmustine, Chlorambucil, Cisplatin, Cyclophosphamide, Dacarbazine, Ifosfamide, Lomustine, Mechlorethamine, Melphalan, Oxaliplatin, Temozolomide, Thiotepa and Trabectedin.
Gpatindia, in a reasonably pertinent field, teaches wherein Busulfan is an alkylating agent (Page 2, Classification).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the alkylating agent of Zhuang with the specific alkylating agent of Gpatindia. Since Gpatindia teaches that Busulfan is an alkylating agent, which is reasonably pertinent to the alkylating agent of Zhuang, one of ordinary skill in the art would combine the two teachings with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to combine these references given the knowledge that Busulfan is an alkylating agent (Gpatindia, Page 2, Classification).
Response to Arguments
Applicant's arguments filed March 17th, 2026 have been fully considered but they are not persuasive.
The Applicant first provides a short summary of the Examiner’s previous rejections (Pages 7 and 8 of the Remarks filed March 17th, 2026). The Applicant states that they traverse the rejection, and then provide the method as claimed in claims 1, 18, and 28, along with stating that claims 2-17 depend from claim 1 and claim 19 depends from claim 18 (Page 8 of the Remarks filed March 17th, 2026). The Applicant argues that the aspects as underlined in the claim language provided on Page 8 are not taught or suggested by Zhuang alone, or in combination with Stahl or Gpatindia (Page 9 of the Remarks filed March 17th, 2026). The Applicant then provides a short summary of aspects of the invention as described in the instant disclosure, arguing that the cited art fails to teach fragmented nucleic acid, or using at least two anchoring agents (one that can hybridize with the nucleic acid and one that forms a covalent bond with the nucleic acid) (Page 9 of the Remarks filed March 17th, 2026). The Applicant provides information and citations from Zhuang, arguing that Zhuang provides no teaching to combine an anchor probe with an alkylating agent for use in anchoring fragmented nucleic acid (Page 9 of the Remarks filed March 17th, 2026). The Applicant further argues that the teachings of Stahl and Gpatindia do not cure the deficiencies of Zhuang (Pages 9 and 10 of the Remarks filed March 17th, 2026).
In response to these arguments, it is noted that the prior art of Qiagen has been introduced to teach on the amended fragmented nucleic acids. Given that the recitation of a fragmented target nucleic acid is obvious in view of Qiagen, the arguments directed towards the previous prior art not teaching on aspects of the invention related to fragmented nucleic acids are not found persuasive.
In regards to the argument that Zhuang does not teach combining an anchor probe with an alkylating agent for anchoring fragmented nucleic acid, fragmented nucleic acids have already been rendered obvious. Furthermore, as indicated above and restated here, the courts have stated, “[i]t is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." (see MPEP 2144.06). Because both the anchor probe and alkylating agent of Zhuang can anchor nucleic acids, it is obvious to combine them for use for the same purpose. Therefore, this argument is not found persuasive.
Conclusion
All claims stand rejected.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Allison E Schloop whose telephone number is (703)756-4597. The examiner can normally be reached Monday-Friday 8:30-5 ET.
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/ALLISON E SCHLOOP/Examiner, Art Unit 1683
/Robert T. Crow/Primary Examiner, Art Unit 1683
Prosecution Insights