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 .
Claim Status
Claims 37-46,48-69 and 71 are pending and under examination. Claims 47 and 70 have been cancelled. Claims 37-39, 44, 46, 48, 50, 51, 58, 61, and 64 have been amended. Claim 37 is the only independent claim.
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. The broadest reasonable interpretation of a claim element (also commonly referred to as a claim limitation) is limited by the description in the specification. The terms “optical barcode” and “optically detectable label” are interpreted under the broadest reasonable interpretation to be:
Optical Barcode – A nucleic acid construct expressed in a cell comprising an ordered series of segments, wherein each segment comprises one or a set of possible nucleic acid sequences each detectable by a corresponding probe carrying a distinct optically detectable label, such that detection of the labeled probes provide an optical signal corresponding to the nucleic acid construct.
Optically detectable label – a fluorophore, or combination of fluorophores producing a distinguishable pseudo-color, conjugated to a probe such that it produces a detectable fluorescent signal upon binding to a corresponding segment of the optical barcode.
Response to Arguments
Priority
Applicant’s arguments regarding entitlement to priority have been considered. With respect to claims 54, 59, and 61-64, Applicant has identified support in the provisional application that adequately describes the claimed subject matter. Specifically, citing the use of FokI as a perturbation agent and describing features and limitations associated with the barcodes corresponding to claims 54, 59, and 61-64. Accordingly 54, 59, and 61-64 are entitled to the benefit of the earlier filing date of the provisional application, March 16, 2015
However, applicant has not provided arguments or identified support for the remaining claims previously listed as lacking entitlement to priority. The examiner has reviewed the provisional application and continues to find that it does not provide written description support for the limitations recited in claims 40, 41, 43, 56, 57, and 71. Accordingly, these claims are not entitled to the benefit of the provisional application filing date and their effective filing date is March 16, 2016.
Objections Withdrawn
The objection to claims 37 and 51 for informalities is withdrawn following the applicants’ amendments.
Objections Maintained
The objection to the specification for improperly demarcated trademarks is maintained. Despite the applicant’s remarks stating the “applicant has submitted herewith a substitute specification in which trademarks have properly demarcated” no substitute specification was attached or listed on the Amendment/Request for Reconsideration.
Rejections Withdrawn
The rejection of claim 47 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 is withdrawn following the applicants’ amendments and cancellation of claim 47.
The rejection of claims 48-50, 56, 61, 64 and 70 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 is withdrawn following the applicants’ amendments and cancelation of claim 70.
The rejection of claims 70 under 35 U.S.C. 103 as being unpatentable over Mhlanga, Lee, and Shopes as applied to claims 37-38, 40-43, 59, 61-62, 64, 66, and 68 above and included here for reasons supra, in further view of Ng et al (“Application of destabilizing sequences on selection marker for improved recombinant protein productivity in CHO-DG44” Metabolic Engineering, 2007, on IDS), is withdrawn following the cancellation of claim 70.
Rejections Maintained
The rejection of claims 39 and 63 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 is maintained.
Applicant's arguments filed 12/15/2025 have been fully considered but they are not persuasive. Applicant asserts that colloidal metals and similar materials are well known in the art as labels for nucleic acid detection, and therefore do not require detailed description under MPEP 2163(II)(A)(1). Applicant’s remarks are directed to the general knowledge that colloidal metals (e.g., gold nanoparticles) may be uses as labels for nucleic acid detection. However, these arguments address only a limited aspect of the rejection and do not fully respond to the basis of the written description rejection.
Specifically, the rejection is not based on whether such materials are known as labels, but rather on the absence of disclosure demonstrating that the inventors were in possession of the claimed use of such materials within the context of the claimed invention. The specification does not describe how such non-nucleic acid-based materials are incorporated into, associated with, or function within the claimed system, which relies on nucleic acid-encoded barcodes and hybridization-based detection.
The rejection is not predicated on whether colloidal metals or quantum dots are known labels, but rather on whether the specification reasonably conveys to one of ordinary skill in the art that the inventors were in possession of the claimed use of such materials within the context of the claimed invention.
The present claims encompass embodiments in which the “optically detectable label” includes non-biological particulate materials, including colloidal metals, quantum dots, nanoshells, and particles defined by size, shape, or refractive index. However, the specification is directed to systems in which, optical barcodes are encoded by nucleic acids, expressed as RNA transcripts, and detected via hybridization of labeled probes (e.g. FISH-based approaches).
The specification does not describe how non-nucleic-acid-based materials such as colloidal metals or quantum dots are incorporated into the claimed system, associated with the nucleic acid barcode, delivered to or localized within cells in a manner consistent with the claimed method, or functionally integrated into the sequential hybridization detection scheme.
While such materials may be generally known as labels, there is no disclosure demonstrating possession of their use within the claimed barcode-encoding and decoding framework, particularly where the barcode is defined as a nucleic acid sequence expressed in cells.
Accordingly, the specification fails to reasonably convey to one of ordinary skill in the art that the inventors had possession of the full scope of the claimed invention, and the rejection under 35 U.S.C. § 112(a)
The rejection of claim 46 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 is maintained.
Applicant's arguments filed 12/15/2025 have been fully considered but they are not persuasive. Applicant amended the claim to recite the “3’ untranslated region (UTR) stem loop from MALAT1 lncRNA transcript.” The Applicant relies on a statement in the specification indicating that the nuclear localization signal may include stem loops from viral transcripts and the lncRNA MALAT1. However, this disclosure is insufficient to support the presently claimed invention.
Claim 46 recites a specific nuclear localization signal, namely “a 3’ untranslated region (UTR) stem loop from MALAT1 lncRNA transcript.” This constitutes a specific species within a broader class of potential localization elements.
The specification does not identify any particular stem loop from MALAT1, nor does it provide sequence information, structural features, or boundaries that would allow one of ordinary skill in the art to recognize which specific MALAT1-derived stem loop encompassed by the claim. Additionally, the specification does not provide any working examples or experimental data demonstrating the use of MALAT1-derived stem loops as nuclear localization signals. Given the structural complexity and size of MALAT1, which contains numerous potential stem-loop structures, the mere reference to MALAT1 does not reasonably convey possession of the specific claimed element (see Fig. 2 below from McCown et al. “Secondary Structural Model of Human MALAT1 Reveals Multiple Structure–Function Relationships, Int. J. Mol. Sci. 2019, 20(22), 5610, which demonstrates the structural complexity of MALAT1). The disclosure does not distinguish among the numerous possible stem loop structures present in MALAT1 nor does it provide guidance for selecting a particular structure corresponding to the claimed limitation.
Accordingly, the specification fails to demonstrate that the inventors were in possession of the claimed subject matter, and the rejection of claim 46 under 35 U.S.C. 112(a) is maintained.
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Fig. 2 McCown et al.
The rejection of Claims 51-55 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 is maintained.
Applicant's arguments filed 12/15/2025 have been fully considered but they are not persuasive.
The applicants amended the claim to change the verbiage and recite that dCas9 is instead a “catalytically inactive nuclease”, which still does not change that claim for which claim 51 depends, requires a nuclease. Nucleases by definition “cleave the phosphodiester bond within a polynucleotide chain”. dCas9 does not have this ability and therefore does not include all of the limitation for which the claim depends, as stated in the previous office action.
The rejection of claims 37-38, 59, 61-62, 64, and 66 under 35 U.S.C. 102(a)(1) as being anticipated by Mhlanga et al (US 2011/0021369 A1, published Jan. 27, 2021, on IDS) is maintained and modified to respond to applicants’ amendments.
The rejection of claims 37- 38, 59, 61-62, 64, and 66 under 35 U.S.C. 102(a)(1) as being anticipated by Mhlanga et al (US 2011/0021369 A1, published Jan. 27, 2021, on IDS) is maintained and modified to respond to applicants’ amendments.
The rejection of claims 37-38, 40-43, 59, 61-62, 64, and 66 under 35 U.S.C. 103 as being unpatentable over Mhlanga, as applied to claims 37-38, 59, 61-62, 64, and 66 above and included here for reasons supra, in view of Lee et al. (“Fluorescent in situ sequencing (FISSEQ) of RNA for gene expression profiling in intact calls and tissues”, Nature Protocols, 2015, on IDS), is maintained and modified to respond to applicants’ amendments.
The rejection of claims 37-38, 40-43, 59, 61-62, 64, 66, and 68 under 35 U.S.C. 103 as being unpatentable over Mhlanga and Lee, as applied to claims 37- 38, 40-43, 59, 61-62, 64, and 66 above and included here for reasons supra, in further view of Shopes et al. (WO 2002/14553 A2, published Feb 21, 2002, on IDS), is maintained and modified to respond to applicants’ amendments.
The rejection of claims 37-38, 40-43, 59, 61-62, 64, 66, and 68 under 35 U.S.C. 103 as being unpatentable over Mhlanga, Lee, and Shopes as applied to claims 37-38, 40-43, 59, 61-62, 64, 66, and 68 above and included here for reasons supra, in further view of Ng et al (“Application of destabilizing sequences on selection marker for improved recombinant protein productivity in CHO-DG44”Metabolic Engineering, 2007, on IDS), is maintained and modified to respond to applicants’ amendments.
Applicant's arguments filed 12/15/2025 have been fully considered but they are not persuasive.
The applicants argue that “Mhlanga teaches inserting constructs including a copy of the promoter sequence of an endogenous gene of interest and a barcode into cells” and that Mhlanga does not teach a genetic perturbation. However, the instant specification states “the genetic perturbation may include a gene knock-in, a gene-knock out, or one or more nucleotide insertions, deletions, substitutions, or mutations.“ (see [0022]). The constructs of Mhlanga include a gene knock-in using a construct with a promoter sequence, GFP, and barcode, or promoter sequence, gene of interest, GFP, and barcode, wherein the barcode represents which construct is introduced, which meet the limitations of a genetic perturbation as described by the specification. Applicants argue that this does not perturb an endogenous gene when inserted into the cell, however, the claims do not require that an endogenous gene is perturbed.
Regarding the amendments to claim 37, Mhlanga teaches embodiments wherein “each cell or cell line having a composition in said polynucleotide(s) which is different from that of the other cell(s) or cell line(s),” wherein the polynucleotide is the vector encoding the promoter sequence, GFP, and optical barcode (see Mhlanga [0131]). Mhlanga further teaches methods in which to achieve individual cells each having different compositions using micro injection (see [0129]-[0130], [0175], [0205], [0258]). Thereby reading on the added limitation of “contacting each cell from a plurality of cells with a different vector”
The applicants further argue that modifying Mhlanga to include a construct comprising genetic perturbations would render Mhlanga unsatisfactory for its intended purpose, and therefore no motivation to combine exists. This argument is unpersuasive and does not overcome the rejection.
It is well established that a prior art reference need not be modified while maintaining its original purpose or function in order to support an obviousness rejection under 35 U.S.C. 103. The relevant inquiry is whether a person of ordinary skill in the art would have had reason to combine teaching of the reference, not whether the resulting modification would preserve the utility of any individual reference in its original context. See In re Kahn, 441 F.3d 977, 988, 78 USPQ2d 1329, 1336 (Fed. Cir. 2006); KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007) (a person of ordinary skill is “not confined” to the purposes disclosed by any particular reference).
Applicant has not demonstrated that the propose combination would render Mhlanga’s teachings of delivering constructs with segmented optical barcodes inoperable or that the art teaches away from the combination. Accordingly, the rejections are maintained for all the claims listed above that are still pending.
Applicants’ request to hold the non-statutory double patenting rejection in abeyance has been considered but is not persuasive.
A rejection based on non-statutory double patenting is properly made during examination to address the issue of claims that are not patentably distinct from claims in a commonly owned patent. Such a reject is not dependent upon the identification of otherwise allowable subject matter and is appropriately maintained at this stage of prosecution. Applicant has not presented arguments addressing the merits of the double patenting rejection. Accordingly, the rejection based on non-statutory double-patenting is maintained.
New Rejections
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 37-46,48-69 and 71 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.
As originally presented in claim set dated 07/26/2021, the claim recited “introducing one or more vectors into the cell or cell population” which encompasses bulk introduction of vectors into a population of cells. Applicant has amended the claims to recite “contacting each cell from a plurality of cells with a different vector,” which requires that individual cells receive distinct vectors. The specification does not reasonably convey to one of ordinary skill in the art that the inventors were in possession of this limitation at the time of filing. While the specification may describe introducing vectors or libraries of constructs into a population of cells, it does not describe or suggest a system in which each individual cell is contacted with a different vector.
The disclosure of introducing multiple vectors into a population is also consistent with cells receiving identical vectors or multiple vectors and does not demonstrate possession of a system in which each cell receives a unique vector. The specification further indicates that the describe methods involve assessing the morphology of a large number of cells per perturbation (e.g. “> 1000 cells of any given perturbation will be imaged” [0056]). This disclosure reflets an experimental design is which multiple cells share the same perturbation, enabling statistical analysis across cell populations. This is inconsistent with the claimed limitation requiring that each individual cell be contacted with different vectors. The specification therefore describes a system is which perturbations are applied to populations of cells, rather than a system in which each cell receives a unique perturbation.
Furthermore, the specification does not describe any methodology, conditions, or controls (e.g. multiplicity of infection or transfection conditions) that would result in or ensure that each cell receives a different vector. The amended limitation represents a specific distribution of vectors across individual cells that is not described in the originally filed disclosure. Accordingly, the specification fails to support the full scope of the claimed invention. Claims 38-46,48-69 and 71 depend on claim 37 and fail to remedy this deficiency and are likewise rejected under 35 U.S.C. 112(a).
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 51-55, and 57 is 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 51 depends from claim 50, which recites “the site-specific nuclease is an RNA-guided DNA endonuclease.” Claim 51 further limits this element to a “catalytically inactive nuclease”, specifically dCas9. A catalytically inactive nuclease, such as dCas9, lacks endonuclease activity and therefore is not an endonuclease. Accordingly, claim 51 introduces a limitation that is inconsistent with the requirements of claim 50. As a result, the scope of the claim is unclear, as it is uncertain whether the claimed enzyme is required to possess endonuclease activity as required by claim 50. Therefore claim 51 fails to particularly point out and distinctly claim the invention. Claims 52- 55 depend on claim 51 and fail to rectify this deficiency and are likewise rejected under 35 U.S.C. 112(b).
Claim 57 recites the limitation "guide RNA" in lines 2 and 3. There is insufficient antecedent basis for this limitation in the claim.
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.
Claims 37-43, 59, 61-64, and 66 under 35 U.S.C. 103 as being unpatentable over Mhlanga, and Lee, as applied to claims 37-38, 40-43, 59, 61-62, 64, and 66 above and included here for reasons supra, and further consideration of the claims.
As stated above, Mhlanga teaches methods disclosed in claim 37, for which claim 39 depends. Mhlanga teaches a “method comprising contacting each cell from a plurality of cells with a different vector comprising nucleic acid sequences encoding i) one or more optical barcodes, wherein each optical barcode comprises a set of ordered segments and each segment comprises a nucleic acid base sequence from a set of possible nucleic acid bases or sequences for that particular segment; and ii) one or more genetic perturbations”(see Mhlanga [0131] (disclosing treating each individual cell with different constructs, also claimed in claim 22),Fig. 1 (depicting gene insert and barcode used for gene knock-in), Fig. 5 (depicting segmented optical barcodes), Fig. 7 (depicting different vectors used)). Mhlanga also teaches “b) incubating the plurality of cells to allow for transcription of RNA comprising the one or more optical barcodes; and c) detecting the one or more optical barcodes in the RNA to identify the one or more genetic perturbations present in the cell” (see Mhlanga [0077]-[0089] (describing the optical barcodes), [0107]-[0110] (describing the inserted marker protein (e.g. gene-knock-in)), [0116]-[0117] (detailing incubation and integration of gene constructs), [0132] (disclosing monitoring probe hybridization to determine which insert is present), [0148]-[0149] (disclosing using multiple beacons to monitor different barcode segments), [0166]-[0178] (disclosing detecting the presence of barcodes with optical labels).
In regards to claim 39, Mhlanga further teaches detecting the one or more optical barcodes in the RNA to identify the one or more genetic perturbations present in the cell. Among those methods, Mhlanga teaches “detecting the one or more optical barcodes comprises: delivering a probe set to the plurality of cells or cell population, each probe in the probe set comprising a sequence that hybridizes to one of the possible nucleic acid sequences at the first segment of the optical barcode on the RNA, wherein different probe sequences are labeled with different optically detectable labels such that each nucleic acid sequence at the first segment of the optical barcode is labeled with a different optically detectable label; determining the nucleotide sequence at the first segment of each barcode by detecting the optically detectable labels; wherein the probes in the probe set bind to the segments of the optical barcode identify each optical barcode and thereby identify the one or more genetic perturbations introduced into each cell or cell population (see Mhlanga Fig. 5). While Mhlanga teaches methods for identifying the barcode, and therefore the gene insert and genetic perturbation in each cell, they do not teach that the optically detectable labels are delivered and determined in a sequential manner.
However, Lee teaches this limitation. Lee teaches fluorescent in situ sequencing (FISSEQ), wherein RNA molecules within intact cells are detected using iterative cycles of biochemical reactions and imaging. In each cycle, optical signals corresponding to nucleotide identity are detected, and the sequence is determined from the ordered series of signals obtained across multiple cycles.
It would have been obvious to one of ordinary skill in the art to apply the sequential, cycle-based optical detection methods of Lee to the barcoded RNA constructs of Mhlanga in order to determine the identity of encoded barcode sequences through iterative detection, as such methods provide a predictable means of decoding nucleic acid sequences within cells while increasing multiplex capacity beyond the 120 possible arrangements of Mhlanga’s simultaneous detection method, while maintaining spatial context. The combination represents a predictable use of known in situ sequencing techniques according to their prior observed functions.
In regards to claim 63, Mhlanga teaches probe sets comprising 3, 4, or 5 distinct optically detectable labels (see Mhlanga Fig. 5)
Claims 37-45, 59, 61-64, and 66 is/are rejected under 35 U.S.C. 103 as being unpatentable over Mhlanga (US 2011/0021369 A1, published Jan. 27, 2021, on IDS) and Lee (“Fluorescent in situ sequencing (FISSEQ) of RNA for gene expression profiling in intact calls and tissues”, Nature Protocols, 2015, on IDS) as applied to claim 37-43, 59, 61-64, and 66 above, and further in view of Cai (US 2014/0031243 A1, published Jan. 30, 2014, on IDS).
In regards to claim 44, as recited above Mhlanga teaches introducing barcoded constructs into cells and detecting optical signals associated with expressed sequences as outlined in claim 37, for which claim 44 depends. Lee, teaches sequential, cycle-based optical detection of RNA sequences within cells using in situ sequencing techniques. However, Mhlanga and Less do not explicitly teach a probe architecture in which an intermediate probe set hybridizes to target RNA and a second probe set bind to the intermediate probes, wherein the second probes carry optically detectable labels.
Wang teaches branched DNA based in situ hybridization methods in which target specific probe sets hybridize to RNA molecules and additional probe sets (including label probes) hybridize to the initial probes, wherein the label probes comprise optically detectable labels that enable detection of the target RNA (see Wang Fig. 1. Thus, Wang teaches probe architecture in which a first set of probes binds to the RNA and a second set of probes binds to the first set and carries detectable labels.
It would have been obvious to one of ordinary skill in the art to incorporate the probe architecture of Wang into the system of Mhlanga as modified by Lee in order to enable flexible probe design and scalable multiplexed optical detection of RNA barcodes. Such probe systems were known to separate target recognition from signal generation and facilitate high-throughput identification of nucleic acid sequences. The combination represents the predictable use of prior art elements according to their established functions to achieve the expected results of detecting nucleic acid sequences within cells.
In regards to claim 45, Wang teaches branched DNA probe architecture in which target-specific probe sets hybridize to RNA molecules and additional probe structures (including preamplifier and amplifier probes) hybridize to the initial probes to form branched complexes. These branched probe structures facilitate binding of multiple labeled probes to a single target-bound probe complex, thereby amplifying the detectable signal. Thus Wang explicitly teaches intermediated probes that are branched and that enable binding of multiple probes carrying optically detectable labels to a single intermediate probe.
Conclusion
No claim is allowed
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 Matthew H Raymonda whose telephone number is (703)756-5807. The examiner can normally be reached Monday - Friday 10:00 am - 4:00 pm.
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/MATTHEW HAROLD RAYMONDA/Examiner, Art Unit 1684 /AARON A PRIEST/Primary Examiner, Art Unit 1681
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