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 .
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-5, 7-8, 12, 14, 18, 22-27, 32, 59, and 78 in the reply filed on 7/6/2026 is acknowledged. Accordingly, claim 79 is withdrawn from consideration as bend drawn to a non-elected invention.
Priority
This application is a 371 of PCT/US2022/076056 filed 09/07/2022 which claims benefit of 63/241,880 filed 09/08/2021.
Information Disclosure Statement
The information disclosure statement (IDSs) submitted on 8/22/2024, 10/31/2025, 4/13/2026 and 7/6/2026 are acknowledged. The submissions are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Drawings
The drawings were received on 3/4/2024. These drawings are found acceptable by the examiner.
Specification
The disclosure is objected to because of the following informalities:
(a) The use of the term “TaqMan” at paragraphs [0015], [0029], [0314], [0327] and [0372], which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore, the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM, or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
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 1-5, 7-8, 12, 14, 18, 22-27, 32, 59, and 78 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.
(a) Claims 1-5, 7-8, 12, 14, 18, 22-27, 32, 59 and 78 are indefinite in the claims 1 and 5 because a nexus between the claimed method steps cannot be ascertained such that one clearly understands how the method is performed to achieve the results of measuring cellular component target expression in cells as instantly claimed. Specifically, the claim does not make clear how the “amplicons of the unique identifier sequence of one or more of the first cellular component-binding reagents” are generated because merely contacting first cellular components-binding reagents with a plurality of cells comprising of cellular components targets wherein the reagent comprise of oligonucleotide comprising a unique identifier” does not necessarily equate to generating amplicons of the unique identifier.
Additionally, the claims are confusing in the claim 1 at the recitation of “predetermined abundance range” because neither the specification nor claims provides limiting definition of terms and one cannot determine the prerequisite required for the claim to functionally properly and thus the metes and bounds of the limitations are unclear. Finally, the claims are indefinite at the recitation of “in a manner configured to achieve an abundance” because the limitation is vague and non-specific and thus it cannot be determined what steps are required in order to perform the functions of achieving abundance. Likewise, it is unclear what threshold is required to establish an abundance range. Clarification is required.
(b) Claim 2 is indefinite and lacks proper antecedent basis at the recitation of “the dynamic range for which acceptable linearity and efficiency of detection” because no limiting definition is provided in the claims or specification for the terms, no prior recitation of any “dynamic range” is provided in the claim 1 from which the claim depends and thus the metes and bounds of the claim limitation in the context of the claim cannot be ascertained.
(c) Claim 5 is indefinite at the recitation of “positive” as it relates to “cellular components target” and “abundance threshold” and the recitation of “negative” as it relates to “cellular component target” and “abundance threshold” because the positive and negative are “relative term”, the specification does not provide a limiting definition of the terms in the context of the claims and thus the metes and bounds of the limitations cannot be ascertained.
(d) Claim 26 contains the trademark/trade name “TaqMan”. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe detection probe and, accordingly, the identification/description is indefinite.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-5, 7, 8, 12, 14, 18, 22-27, 32, 59 and 78 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 5, 6, 10-16, 18, 21-26, 30-31, 33-34, 38, 49-50, 54-59 of copending Application No. 18/836303 in view of Chang (US 20180346970).
Although the claims at issue are not identical, they are not patentably distinct from each other because:
In the instant application, pending claim 1 is directed to a method for measuring cellular component target expression in cells, comprising: contacting a plurality of first cellular component-binding reagents with a first plurality of cells comprising a plurality of cellular component targets, wherein each of the plurality of first cellular component-binding reagents comprises a cellular component- binding reagent specific oligonucleotide comprising a unique identifier sequence for the first cellular component-binding reagent, and wherein the first cellular component- binding reagent is capable of specifically binding to at least one of the plurality of cellular component targets; generating amplicons of the unique identifier sequence of one or more of the first cellular component-binding reagents; determining the amount of one or more amplicons as an indication of the amount of the one or more of the first cellular component-binding reagents; and if the amount of one or more amplicons indicates an abundance of a first cellular component-binding reagent above or below a predetermined abundance range, repeating the contacting step with a second plurality of cells in a manner configured to achieve an abundance of said first cellular component-binding reagent within said predetermined abundance range.
The claim 2 of co-pending application 18/836303 is directed a method for measuring cellular component target expression in cells, comprising: contacting a plurality of first cellular component-binding reagents with a plurality of first detectable conjugates, wherein each of the plurality of first cellular component-binding reagents comprises a cellular component-binding reagent specific oligonucleotide comprising a unique identifier sequence for the first cellular component-binding reagent, and wherein the first cellular component-binding reagent is capable of specifically binding to at least one of a plurality of cellular component targets, and wherein each of the plurality of first detectable conjugates comprises a detectable moiety, or precursor thereof, and a unique identifier specific oligonucleotide comprising a sequence configured to bind a unique identifier sequence, wherein first detectable conjugates capable of binding the same unique identifier sequence comprise the same detectable moiety, or a precursor thereof, and wherein first detectable conjugates capable of binding different unique identifier sequences comprise different detectable moieties, or precursors thereof; contacting the plurality of first cellular component-binding reagents associated with the plurality of first detectable conjugates with a first plurality of cells comprising a plurality of cellular component targets; and measuring emissions of the detectable moiety of each first detectable conjugate with an instrument as an indication of the amount each of first cellular component- binding reagent bound to a cellular component target and a first detectable conjugate. The claims 2-3, 5, 6, 10-16, 18, 21-26, 30-31, 33-34, 38, 49-50, 54-59 of copending application 18/836303 embodies and overlap in scope with the 1-5, 7, 8, 12, 14, 18, 22-27, 32, 59 and 78 of the instant invention.
The recited claim of the instant invention only differs from the claims of copending application 18/836,303 in that the claims 2-3, 5, 6, 10-16, 18, 21-26, 30-31, 33-34, 38, 49-50, 54-59 do not recite generating amplicons of the unique identifier sequence of one or more cellular components binding reagents, wherein the amplification is performed by PCR. Likewise, the claims of the instant invention also does not teach an instrument as a indication of the amount each of the cellular component-binding reagent bound to a cellular component target and detectable conjugate.
Chang (US 20180346970) teaches methods for simultaneously measuring protein expression and gene expression in single cells using antibody conjugate oligonucleotides and barcoded oligos attached to solid support beads (entire document, FIG. 2 and FIG. 8 for examples). Chang teaches a method for simultaneous measurement of protein and gene expressions in cells, comprising: contacting a plurality of cellular component-binding reagents ([570]; FIG. 6, 605a-c) with a plurality of cells ([570]; FIG. 6, 610) comprising a plurality of cellular component targets ([570] lines16-21; FIG. 6) and copies of a nucleic acid target ([570]; FIG. 6, 630), wherein the nucleic acid target comprises mRNA ([570]; FIG. 6, 630), wherein each cellular component-binding reagent of the plurality of cellular component-binding reagents comprises a cellular component-binding reagent specific oligonucleotide comprising a unique identifier for the cellular component-binding reagent (FIG. 4, antibody specific oligonucleotide sequence; [0530]; [0522]) and a poly(A) sequence 18-30 nucleotides in length (FIG. 4; [0530]; [0522]”the poly(A) tail can be 18 nucleotides in length”), wherein the cellular component-binding reagent specific oligonucleotide comprises DNA ([0611]; [0530]; [0522]; [0570]; [0609]), and wherein the cellular component-binding reagent is capable of specifically binding to at least one of the plurality of cellular component targets ([570] lines 11-14; FIG. 6); partitioning the plurality of cells associated with the cellular component-binding reagents to a plurality of partitions ([570] lines 23-26; FIG. 6); wherein a partition of the plurality of partitions comprises a single cell from the plurality of cells associated with the cellular component- binding reagents ([570]; FIG. 6); in the partition comprising the single cell, contacting a solid support comprising a plurality of oligonucleotide barcodes with the cellular component-binding reagent specific oligonucleotides and the copies of the nucleic acid target for hybridization([570]; FIG. 6), wherein the oligonucleotide barcodes each comprise a poly(T) sequence, a first universal sequence, a first molecular label ([0613]). Chang et al further linear amplification to generate amplicons for sequencing, wherein the method comprises amplification by PCR and hybridization using fluorescent probes ([0293], [0495] and [0715])); obtaining sequence information of the plurality of separated extended cellular component-binding reagent specific oligonucleotides, or products thereof, to determine the number of copies of at least one cellular component target of the plurality of cellular component targets in one or more of the plurality of cells ([0570] page 63, left-hand col, lines18-26; [0407] and [0514] discloses using barcodes to determine target copy number; [0766]); and obtaining sequence information of the plurality of separated barcoded nucleic acid molecules or products thereof using cytometry information ([0102], [0122] and [0649]).
It would have been obvious to one of ordinary skill in the art at the time of the effective filing date of the claimed invention to have combined the claims of 18/836303 with the teachings of Chang to encompass steps of amplification and cytometry for the obvious benefit of measuring cellular components target expression in cells as taught Chang et al. The combination of claims and prior art provides prima facie case of obviousness.
This is a provisional nonstatutory double patenting rejection.
Closest Prior Art Rejection
9. The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Chang (US 20180346970) teaches methods for simultaneously measuring protein expression and gene expression in single cells using antibody conjugate oligonucleotides and barcoded oligos attached to solid support beads (entire document, FIG. 2 and FIG. 8 for examples).
Chang teaches a method for simultaneous measurement of protein and gene expressions in cells, comprising: contacting a plurality of cellular component-binding reagents ([570]; FIG. 6, 605a-c) with a plurality of cells ([570]; FIG. 6, 610) comprising a plurality of cellular component targets ([570] lines16-21; FIG. 6) and copies of a nucleic acid target ([570]; FIG. 6, 630), wherein the nucleic acid target comprises mRNA ([570]; FIG. 6, 630), wherein each cellular component-binding reagent of the plurality of cellular component-binding reagents comprises a cellular component-binding reagent specific oligonucleotide comprising a unique identifier for the cellular component-binding reagent (FIG. 4, antibody specific oligonucleotide sequence; [0530]; [0522]) and a poly(A) sequence 18-30 nucleotides in length (FIG. 4; [0530]; [0522]”the poly(A) tail can be 18 nucleotides in length”), wherein the cellular component-binding reagent specific oligonucleotide comprises DNA ([0611]; [0530]; [0522]; [0570]; [0609]), and wherein the cellular component-binding reagent is capable of specifically binding to at least one of the plurality of cellular component targets ([570] lines 11-14; FIG. 6); partitioning the plurality of cells associated with the cellular component-binding reagents to a plurality of partitions ([570] lines 23-26; FIG. 6); wherein a partition of the plurality of partitions comprises a single cell from the plurality of cells associated with the cellular component- binding reagents ([570]; FIG. 6); in the partition comprising the single cell, contacting a solid support comprising a plurality of oligonucleotide barcodes with the cellular component-binding reagent specific oligonucleotides and the copies of the nucleic acid target for hybridization([570]; FIG. 6), wherein the oligonucleotide barcodes each comprise a poly(T) sequence, a first universal sequence, a first molecular label ([0613]), and a cleavage region ( [0502]lines 1-4, [0473] substrate is a bead; see also [0852] which references 15/605,874, which teach “a cleavable linker or modified nucleotide can be part of the universal label sequence to enable the stochastic barcode to be cleaved off from the support” in para [0182]), wherein the cleavage region is 5' of the first universal sequence and comprises one or more cleavage sites (FIG. 1; [0400]; [0455]” A barcode can comprise a 5′ amine region attached to a bead”; [0181]; [0073] teaches amine can be substituted with UV photocleavable group or disulfide linkage on a particle; [0502] further teaches “a nucleic acid can be removed from a substrate through a restriction endonuclease digestion,” thus a restriction site of a restriction enzyme could have been used as simple substitution of 5’ amine group); extending the cellular component-binding reagent specific oligonucleotides (FIG. 6, sample indexing oligo is barcode attached to antibody, see [0005]” sample indexing composition of the plurality of sample indexing compositions comprises two or more antigen binding reagents (e.g., protein binding reagents and antibodies), wherein each of the two or more antigen binding reagents is associated with a sample indexing oligonucleotide”; [0610] ) hybridized to the plurality of oligonucleotide barcodes ([0610], barcoded sample indexing oligonucleotides; FIG. 8A1); extending the plurality of oligonucleotide barcodes hybridized to the copies of a nucleic acid target (FIG. 2; FIG. 6; [0570]); obtaining sequence information of the plurality of separated extended cellular component-binding reagent specific oligonucleotides, or products thereof, to determine the number of copies of at least one cellular component target of the plurality of cellular component targets in one or more of the plurality of cells ([0570] page 63, left-hand col, lines18-26; [0407] and [0514] discloses using barcodes to determine target copy number; [0766]); and obtaining sequence information of the plurality of separated barcoded nucleic acid molecules, or products thereof, to determine the copy number of the nucleic acid target in one or more of the plurality of cells ([0570] page 63, left-hand, col, lines 18-26; [0407] and [0514] discloses using barcodes to determine target copy number; [0766]). While Chang teaches multiple embodiments of the claimed invention, Chen does not teach combination of method steps recited therein.
Conclusion
10. No claims are allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to CYNTHIA B WILDER whose telephone number is (571)272-0791. The examiner can normally be reached Flexible.
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/CYNTHIA B WILDER/Primary Examiner, Art Unit 1681
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