DETAILED ACTION
Election/Restrictions
Applicant’s election of species (1) (at least one cellular component is intracellularly distributed, see claims 2, 37, and 41), species (4) (at least one barcode comprises exogenous elements in a cell, see claims 5 and 19), species (6) (the recognition sequence comprises a protein or one or more repeated amino acid sequences, see claims 12-14), species (7) (one or more barcodes are linked to one or more scaffold proteins capable of localizing the barcodes, see claim 33), and the barcodes are expressed under control of constitutively active promoter sequences in claim 25 in the reply filed on October 13, 2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)). Claims 1, 2, 4-9, 12-14, 19, 20, 22, 23, 25-27, 33, 37, 38, 41, 45-47, 56, and 57 will be examined.
Drawings
Some words or numbers in Figures 1, 4-6, and 11 cannot be recognized. Applicant is required to submit new Figures 1, 4-6, and 11 in response to this office action. No new matter may be introduced in the required drawing. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d).
Claim Objections
Claim 1 is objected to because of the following informality: “each barcode” should be “each of the barcodes”.
Claim 2 is objected to because of the following informality: “at least one cellular component” should be “at least one of the cellular components”.
Claim 4 or 5 is objected to because of the following informality: “at least one barcode” should be “at least one of the barcodes”.
Claim 5 is objected to because of the following informality: “a cell” should be deleted.
Claim 6 is objected to because of the following informality: “the one or more barcode elements” should be “the one or more of the endogenous or exogenous elements”.
Claim 19 or 23 is objected to because of the following informality: “the cell” should be “the one or more cells”.
Claim 27 is objected to because of the following informality: “one or more detection site” should be “one or more detection sites”.
Claim 37 is objected to because of the following informality: “one or more cellular components” should be “the one or more cellular components”.
Claim 41 is objected to because of the following informality: “one or more cellular components of cells” should be “the one or more cellular components of the cells”.
Claim 56 is objected to because of the following informality: “detecting the one or more barcodes” should be “said detecting each of the barcodes”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
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 1-9, 12-14, 19, 20, 22, 23, 25-27, 33, 37, 38, 41, 45-47, 56, and 57 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.
Claim 1 is rejected as vague and indefinite. Since the claim does not indicate how one or more barcodes enter one or more cells and how the one or more barcodes enter locations of one or more cell components, it is unclear why each of the barcode can be localized at a site of a cellular component of the one or more cellular components, why each of the barcodes and its location in the one or more cells can be detected, and why one or more locations of each of the barcodes can be recorded such that the spatial distribution of the one or more cellular components cannot be mapped. Please clarify.
Claim 7 is rejected as vague and indefinite. Since claim 6 requires that the barcode recognition sequences are portions of the one or more barcode elements, if the one or more barcode elements in claim 7 is identical to the one or more barcode elements in claim 6, it is unclear why the barcode recognition sequences can be adjacent to or can be flanked by one or more barcode elements capable of recruiting a molecule capable changing the barcode elements. Please clarify.
Claim 9 or 12 or 13 recites the limitation “the recognition sequence” in the claim. There is insufficient antecedent basis for this limitation in the claim because there is no phrase “a recognition sequence” in claim 1. Please clarify.
Claim 22 is rejected as vague and indefinite. Since claim 1 does not have the phrase “one or more barcode elements”, it is unclear why one or more barcode elements can be error correction elements in claim 22. Please clarify.
Claim 23 is rejected as vague and indefinite. Since claim 1 does not require that the barcodes are DNA fragments in a vector transformed or transfected to the one or more cells, it is unclear why the barcodes can be expressed in the cell wherein the barcodes are expressed as RNA and translated to protein. Please clarify.
Claim 25 is rejected as vague and indefinite. Since claim 1 does not require that the barcodes are DNA fragments located at downstream of constitutively active promoter sequences, cell-specific promoter sequences, drug-inducible, light-inducible, or temperature-dependent promoter-sequences, or any combination thereof in a vector, it is unclear why the barcodes can be expressed under control of constitutively active promoter sequences, cell-specific promoter sequences, drug-inducible, light-inducible, or temperature-dependent promoter-sequences, or any combination thereof. Please clarify.
Claim 26 or 38 is rejected as vague and indefinite because it is unclear what is the relationship between two or more cells in the claim and one or more cells in claim 1. Please clarify.
Claim 38 recites the limitation “the intercellular and/or intracellular one or more barcode elements” in the claim. There is insufficient antecedent basis for this limitation in the claim because there is no phrase “intercellular and/or intracellular one or more barcode elements” in claim 1. Furthermore, since the word “intracellular” means “located or occurring within a cell or cells” (see the definition for “intracellular”), it is unclear why intracellular one or more cellular components can be spatially distributed between two or more cells in a population. Please clarify.
Claim 41 recites the limitation “the recording and mapping of intercellular and/or intracellular spatial distribution of one or more cellular components of cells” in the claim. There is insufficient antecedent basis for this limitation in the claim because there is no phrase “recording and mapping of intercellular and/or intracellular spatial distribution of one or more cellular components of cells” in claim 1. Please clarify.
Claim 45 or 46 recites the limitation “the probes” in the claim. There is insufficient antecedent basis for this limitation in the claim because there is no word “probes” in claim 1. Please clarify.
Claim 47 recites the limitation “the one or more probes” in the claim. There is insufficient antecedent basis for this limitation in the claim because there is no phrase “one or more probes” in claim 1. Please clarify.
Claim 56 is rejected as vague and indefinite because it is unclear that detecting the one or more barcodes comprises sequential rounds of imaging what, sequencing what, and mass spectrometry of what. Please clarify.
Claim 57 is rejected as vague and indefinite. Since claim 1 does not contain a phrase “barcoded cellular components” and does not indicate what is the relationship between one or more cells in claim 1 and a cell line in claim 57, it is unclear why barcoded cellular components can pass through a cell line to one or more progeny cells. Please clarify.
Claim Rejections - 35 USC § 102
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.
Claims 1, 2, 4-6, 20, 27, 33, and 37 are rejected under 35 U.S.C. 102 (a) (1) as being anticipated by Nakamoto et al., (US 2020/0248263 A1, published on August 6, 2020).
Regarding claims 1, 2, 4-6, 20, 27, 33, and 37, Nakamoto et al., teach a method for mapping spatial distribution of one or more cellular components comprising: providing one or more cells; providing one or more barcodes (ie., barcodes hybridized to cellular component-binding reagent specific oligonucleotides wherein each of the cellular component-binding reagent specific oligonucleotides comprises a detectable moiety and a unique identifier sequence for the cellular component-binding reagent capable of specifically binding to the at least one cellular component), wherein each of the barcodes identifies a cell or cellular component in the one or more cells; localizing each of the barcodes to a site of a cellular component (ie., by images); detecting each of the barcodes and its location in the one or more cells (ie., by detectable signals); and recording one or more locations of each of the barcodes to map the spatial distribution of the one or more cellular components (ie., by correlating the images showing the locations of the cellular components with an image of a sample such as a cell) as recited in claim 1 wherein at least one of the cellular components is intracellularly distributed as recited in claim 2, at least one of the barcodes comprises one or more barcode elements (ie., an identifier sequence for the cellular component-binding reagent) as recited in claim 4, at least one of the barcodes comprises endogenous or exogenous elements in a cell as recited in claim 5, the elements comprise barcode recognition sequences (ie., a molecular label sequence) that are recognized by one or more recognition molecules as recited in claim 6, the barcodes comprise unique combinations of barcode elements as recited in claim 20, the barcodes comprise one or more orthogonal barcode sets, wherein each barcode in the barcode set comprises one or more detection site that differs in binding from the one or more binding sites of a different barcode (ie., a plurality of barcodes with distinct sequences or unique sequences) as recited in claim 27, the one or more barcodes are linked to one or more scaffold proteins (ie., GFP as a detectable moiety located on barcodes hybridized to cellular component-binding reagent specific oligonucleotides) as recited in claim 33, and the method further comprises mapping intercellular spatial distribution of one or more cellular components as recited in claim 37 (see paragraphs [0006], [0007], [0009], [0014], [0098], [0237], [0294], and [0403] to [0409]).
Therefore, Nakamoto et al., teach all limitations recited in claims 1, 2, 4-6, 20, 27, 33, and 37.
Claim Rejections - 35 USC § 103
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.
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 19 and 22 are rejected under 35 U.S.C. 103 as being unpatentable over Nakamoto et al., as applied to claims 1, 2, 4-6, 20, 27, 33, and 37 above, and further in view of Salk et al., (US 2021/0010065 A1, priority date: March 15, 2018).
The teachings of Nakamoto et al., have been summarized, supra.
Nakamoto et al., do not disclose that each of the barcodes is an exogenous set synthesized outside the cells as recited in claim 19 and one or more barcode elements are error correction elements as recited in claim 22.
Salk et al., teach that a barcode can be either endogenous or exogenous and is able to be used for error correction (see abstract and paragraphs [0077], [0209], and [0251]).
Therefore, it would have been prima facie obvious to one having ordinary skill in the art at the time the invention was made to have performed the methods recited in claims 19 and 22 wherein each of the barcodes is an exogenous set synthesized outside the cells and one or more barcode elements are error correction elements in view of the prior arts of Nakamoto et al., and Salk et al.. One having ordinary skill in the art would have been motivated to do so because Salk et al., teach that a barcode can be either endogenous or exogenous and is able to be used for error correction (see abstract and paragraphs [0077], [0209], and [0251]). One having ordinary skill in the art at the time the invention was made would have a reasonable expectation of success to perform the methods recited in claims 19 and 22 using an exogenous barcode set comprising error correction elements in view of the prior arts of Nakamoto et al., and Salk et al., such that the barcodes recited in claim 1 have an ability to be used for error corrections.
Conclusion
Since the claims in this instant application is so vague and indefinite (see above objections and the rejections under 35 U.S.C. 112 (b)), applicant is required to amend above objected and rejected claims in response to this office action such that the office can conduct a better prior art search.
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Frank Lu, Ph. D., whose telephone number is (571)272-0746. The examiner can normally be reached Monday to Friday, 9 AM to 5 PM.
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/FRANK W LU/
Primary Examiner, Art Unit 1683
January 5, 2026