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. Priority This application is a 371 of PCT/US2021/019596 filed 02/25/2021 . PCT/US2021/019596 has PRO 62/985,849 filed 03/05/2020 . All claims are examined using the earlier filing date. Claim Status Claims 1-40 were cancelled prior to examination. Claims 41-60 are pending and under examination. Claim 41 is the only independent claim. Specification Applicant is reminded of the proper content of an abstract of the disclosure. A patent abstract is a concise statement of the technical disclosure of the patent and should include that which is new in the art to which the invention pertains. The abstract should not refer to purported merits or speculative applications of the invention and should not compare the invention with the prior art. If the patent is of a basic nature, the entire technical disclosure may be new in the art, and the abstract should be directed to the entire disclosure. If the patent is in the nature of an improvement in an old apparatus, process, product, or composition, the abstract should include the technical disclosure of the improvement. The abstract should also mention by way of example any preferred modifications or alternatives. Where applicable, the abstract should include the following: (1) if a machine or apparatus, its organization and operation; (2) if an article, its method of making; (3) if a chemical compound, its identity and use; (4) if a mixture, its ingredients; (5) if a process, the steps. Extensive mechanical and design details of an apparatus should not be included in the abstract. The abstract should be in narrative form and generally limited to a single paragraph within the range of 50 to 150 words in length . See MPEP § 608.01(b) for guidelines for the preparation of patent abstracts. The abstract of the disclosure is objected to because it is fewer than 50 words in length . A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b). Claim Rejections - 35 USC § 112 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. Claims 41-60 are 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. The claims recite “( b) contacting a biological sample with an oligonucleotide blocking agent ” however, the specification does not describe the use of oligonucleotide blocking agents. Instead, the specification uses two example blocking agents s uch as Fc receptor blockers (Fc Block) and monocyte blocker (see [0109]) , which are protein-based reagents that prevent nonspecific protein interactions. The specification does not describe or provide working examples of oligonucleotides functioning as blocking agents, nor agents blocking oligonucleotides that would reduce undesired interactions in the claimed method. Accordingly, the specification does not reasonably convey to one of ordinary skill in the art that the inventors had possession of the claimed subject matter. 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 appl icant regards as his invention. Claim 41-60 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. Specifically, c laim 41 FILLIN "Enter claim identification information" \* MERGEFORMAT recites in step (a) “contacting the sample with a permeabilization buffer,” and in step (b) “contacting a biological sample with an oligonucleotide blocking agent.” It is unclear whether the “sample” of step (a) is the same as the “biological sample” of step (b) or if two separate samples are intended. The subsequent steps (c) , (d) , and (e) refer to “the biological sample,” which appears to rely on the introduction of “a biological sample” in step (b) rather that the “sample” introduced in step (a). Accordingly the scope of the claim is unclear as to whether the recited method is performed on a single sample or multiple samples. Additionally, the term “oligonucleotide blocking agent” in claim 40 is unclear. Under a first reasonable interpretation, the term refers to an oligonucleotide that functions as a blocking agent. Under a second reasonable interpretation, the term refers to an agent that blocks oligonucleotide interactions, such as preventing hybridization or nonspecific binding of oligonucleotide-based constructs, regardless of whether the agent itself is an oligonucleotide. These interpretations result in materially different scopes, as the first interpretation limits the blocking agent to oligonucleotides, whereas the second interpretation encompasses a broader class of agents, including proteins and other molecules that interact with oligonucleotides. The specification does not resolve this ambiguity. The specification uses example blocking agents such as Fc block and monocyte blocker , which are protein-based reagents, and does not clearly describe or define an “oligonucleotide blocking agent” or explain whether the blocking agent must itself be an oligonucleotide or instead acts on oligonucleotides. Accordingly, one of ordinary skill in the art would not be able to determine the metes and bounds of the claimed invention with reasonable certainty. A rejection under 35 U.S.C. 112(b) is valid when two interpretations are present. See Ex parte Miyazaki, 89 USPQ2d 1207 (BPAI 2008) ("[R] ather than requiring that the claims are insolubly ambiguous, we hold that if a claim is amenable to two or more plausible claim constructions, the USPTO is justified in requiring the applicant to more precisely define the metes and bounds of the claimed invention by holding the claim unpatentable under 35 U.S.C. §112, second paragraph, as indefinite."). Claims 42-60 are rejected under 35 U.S.C. 112(b) for the same reasons as claim 41, from which they depend. None of the dependent claims clarify whether the “sample” recited in step (a) and the “biological sample” recited in step (b) refer to the same sample or to different samples. Accordingly, the scope of each of the dependent claims remains indefinite. Claim 46 recites “ a unique molecular identifier that is positioned adjacent to the barcode on its 5' or 3' end ,” however claim 41 recites multiple barcodes sequences, including barcode sequence associated with a first construct and a barcode sequence associated with at least one additional construct. It is therefore unclear which barcode is being referred to by “the barcode” or whether the limitation applies to one or more of the recited barcode sequences. Accordingly, the scope of the claim is not reasonably certain. Claim 47 recites the limitations “the anchor sequence” in line 1 and " FILLIN "Enter appropriate information" \* MERGEFORMAT the capture oligonucleotide sequence " in line 2. There is insufficient antecedent basis for either of these limitations in the claim. Claim 48 recites “the capture oligonucleotide’ in line 1 and “the anchor sequence” and “amplification handle” in line 2. The is insufficient antecedent basis for either of these limitations in the claim. Claim 59 depends on claim 48 and fails to rectify this deficiency and is likewise rejected. Claim 53 recites the limitation “the capture sequence” in lines 1 and 2. There is insufficient antecedent basis for this limitations in the claim. Claim 54 depends on claim 53 and fails to rectify this deficiency and is likewise rejected. Claim Interpretation The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art. For purposes of examination, the term “oligonucleotide blocking agent” is interpreted under the broadest reasonable interpretation as an agent that reduces or prevents undesired interactions involving oligonucleotides, such as nonspecific hybridization or binding oligonucleotide-based constructs withing a biological sample. This interpretation is consistent with the specification, which states “ the hybridization buffer composition may inhibit non-specific binding of construct compositions to biomolecules ” (see [0021]). Claim Rejections - 35 USC § 103 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 ( i.e., changing from AIA to pre-AIA ) 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. 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. Claim(s) 41-60 are rejected under 35 U.S.C. 103 as being unpatentable over FILLIN "Insert the prior art relied upon." \d "[ 2 ]" Stoeckius et al. (US 2018/0251825 A1, published Sep. 6, 2018 , on IDS 04/02/2024) in view of Lundorf et al. (US 2018/ 0340174 Al, published Nov. 29, 2018). Stoeckius is in the field of detecting the presence of molecules in a sample, and teaches using oligonucleotide-labeled ligands to detect targets in a sample. In regards to claim 1, Stoeckius teaches “ a method of detecting one or more targets in a sample, comprising:(a) contacting the sample with a permeabilization buffer (see Stoeckius [0126], [0404], [0457], ; (c) contacting the biological sample with a composition comprising a first construct that comprises a first ligand attached or conjugated to a polymer construct by a linker, said first ligand binding specifically to a first target, wherein the polymer construct comprises a barcode sequence that specifically identifies the first ligand (see Stoeckius [0009], [0013]) ; (d) contacting the biological sample with a composition comprising at least one additional construct, which construct comprises an additional ligand attached or conjugated to an additional polymer construct by a linker, said additional ligand binding specifically to an additional target, wherein the additional polymer construct comprises a barcode sequence that specifically identifies the additional ligand (see Stoeckius [0011], [0013]) ; and (e) detecting the barcode sequences to identify whether the biological sample expresses or contains the first target, the additional target, or a combination of the first target and additional target (see Stoeckius [0013] ) . However Stoeckius does not explicitly teach contacting the biological sample with an oligonucleotide blocking agent. Lundorf is similarly in the field of identifying molecules in a sample a nd teaches the use of many different blocking agents in nucleic acid-based assays to reduce undesired interactions including nonspecific hybridization, in complex biological systems. (see Lundorf [0211] , [3495] ). Among the blocking agents taught by Lundorf are “ oligonucleotide, such as a single- or double- or triple or quadruple-stranded DNA or RNA or modified DNA or modified RNA or DNA mimic or RNA mimic ” as well as “ an enzyme, a structural protein, a receptor. “ (see Lundorf [0255], [3495]). Lundorf further teaches the use of modified oligonucleotides, including phosphorthioate -modified nucleotides, to improve oligonucleotide stability and performance in such environments (see Lundorf [0154], [3483] ). It would have been prima facie obvious to one of ordinary skill in the art at the time of filing to include an oligonucleotide blocking agent in the method of Stoeckius , as taught by Lundorf , in order to reduce nonspecific interactions and improve detection specificity. It would have been further obvious to utilize phosphorothioate -modified oligonucleotides as such blocking agents to improve their stability and persistence in the biological sample as taught by Lundorf . The combination represents the predictable use of prior art elements according to their established functions. In regards to claim 42, Stoeckius teaches detecting intracellular targets (see Stoeckius [0105], [0126], [0440]). In regards to claim 43, Stoeckius teaches detecting cell surface targets (see Stoeckius [0013], [0015], [0021]). In regards to claim 44, Stoeckius teaches detecting targets that are either protein of nucleic acids (see Stoeckius Fig. 1, [0029]). In regards to claim 45, Stoeckius teaches the polymer constructs comprise an amplification handle and an anchor for hybridizing to a capture sequence that comprises a sequence complementary to said anchor (see Stoeckius [0009], [0013]). In regards to claim 46, Stoeckius teaches unique molecular identifier that is positioned adjacent to the barcode on its 5' or 3' end (see Stoeckius [0009], [0013]). In regards to claim 47, Stoeckius teaches hybridizing each Anchor sequence in individual constructs to a capture sequence prior to detection (see Stoeckius [0013]). In regards to claim 48, Stoeckius teaches extending the capture oligonucleotide hybridized to the anchor sequence to copy the construct barcode and amplification handle onto the double stranded sequences prior to the detecting (see Stoeckius [0013]). In regards to claim 49, Stoeckius teaches the sample is a biological sample (see Stoeckius [0013]). In regards to claim 50, Stoeckius teaches the ligand is an antibody or fragment thereof (see Stoeckius Fig. 1, Fig. 5, [0033], [0045]). In regards to claim 51 and 52 , Lundorf teaches the use of modified oligonucleotides as blocking agents (see Lundorf [0211], [0254]-[0255], [3495]). Lundorf further teaches modified oligonucleotides comprising phosphorothioated oligonucleotides which (see Lundorf [0154] ). It would have been prima facie obvious to one of ordinary skill in the art at the time of filing to incorporate the phosphorothioated nucleic acids into the blocking agents to improve o ligonucleotide stability and performance in complex biological environments. Lundorf further teaches that blocking agents in a nucleic acid-based assay may include proteins (see Lundorf [ 0 255]). It is well known in the art that single-stranded binding proteins bind to single-stranded nucleic acids and prevent undesired interactions such as reannealing and nonspecific hybridization. Accordingly, it would have been obvious to one of ordinary skill in the art to utilize single-stranded binding proteins as a type of protein blocking agent in order to reduce undesired nucleic acid interactions. In regards to claim 53, Stoeckius teaches methods where the capture sequence is immobilized on a substrate (see Stoeckius [0091]). In regards to claim 54, Stoeckius teaches the substrate is a bead, a slide, a multi-well plate, a microwell, a nanowell , or a chip. (see Stoeckius [0095]). In regards to claim s 55 and 60 , Stoeckius teaches sample comprises or is a population of the same or a mixture of different cells, cell or cell membrane components, tissue, or a lysate of said cells or tissue (see Stoeckius [0014]) . In regards to claim 56, Stoeckius teaches fixation procedures before the contacting step or between sequential contacting steps with first or additional constructs (see Stoeckius [0126], [0440]). In regards to claim 57, Stoeckius teaches a washing step (see Stoeckius Fig. 1, [0013]). In regards to claim 58, Stoeckius teaches determining the expression level of the first target or additional target in the sample by detecting the amount of the corresponding construct barcodes normalized by the amount of any one of unique molecular identifiers or the mean amount of two or more of unique molecular identifiers (see Stoeckius [0013]). In regards to claim 59, Stoeckius teaches amplifying the double strand oligonucleotide sequences with primers annealed to the amplification handles (see Stoeckius [0014]). Conclusion No claim is allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT Matthew H Raymonda whose telephone number is FILLIN "Phone number" \* MERGEFORMAT (703)756-5807 . The examiner can normally be reached FILLIN "Work Schedule?" \* MERGEFORMAT Monday - Friday 10:00 am - 4:00 pm . Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, FILLIN "SPE Name?" \* MERGEFORMAT Heather Calamita can be reached at FILLIN "SPE Phone?" \* MERGEFORMAT 571-272-2876 . The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /MATTHEW HAROLD RAYMONDA/ Examiner, Art Unit 1684 /AARON A PRIEST/ Primary Examiner, Art Unit 1681