DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
The Track One Request, filed 01/15/2025, was granted 02/25/2025. Therefore, this application is accorded special status.
Amendments and Status of the Claims
This action is in response to papers filed 21st April 2026, in which claims 1 and 21 were amended, no claims were canceled, and no new claims were added. Claim 5 was previously cancelled. All of the amendments have been thoroughly reviewed and entered.
Applicant has amended:
i) claims 1 and 21 to overcome §102 and 103 rejections; the rejections are withdrawn. However, new 103 rejection has been presented in this office action addressing amendments.
Applicant’s arguments, see pg. 5 onwards, also filed 21st April 2026, with respect to:
rejections of claims 1-4 and 6-25 under 35 USC § 102 and 103 have been fully considered and are persuasive.
Objections and Rejections not reiterated here are withdrawn.
Claims 1-4 and 6-25 are under consideration.
Priority
This application is a continuation of U.S. patent application Ser. No. 18/643,870 filed on Apr. 23, 2024 which is a continuation of U.S. patent application Ser. No. 16/551,638, filed on Aug. 26, 2019, now U.S. Pat. No. 11970737, which is a continuation of U.S. patent application Ser. No. 16/219,553, filed on Dec. 13, 2018, now U.S. Pat. No. 10,392,661, which is a continuation of U.S. patent application Ser. No. 16/038,832, filed on Jul. 18, 2018, now U.S. Pat. No. 10,202,646, which is a continuation of U.S. patent application Ser. No. 15/224,460, filed on Jul. 29, 2016, now U.S. Pat. No. 10,047,394, which is a continuation of U.S. patent application Ser. No. 14/281,706, filed on May 19, 2014, now U.S. Pat. No. 9,816,137, which is a continuation of U.S. patent application Ser. No. 12/969,581, filed on Dec. 15, 2010, now U.S. Pat. No. 8,835,358, which claims priority to U.S. Provisional Application No. 61/286,768, filed on Dec. 15, 2009.
Accordingly, claims 1 -4 and 6- 25 have an effective filing date of Dec. 15, 2009, which is the filing date of the earliest priority document.
Claim Interpretation
It is noted that claims 1 and 21 are broad and do not limit the label, universal primer, or biotin-tagged oligonucleotide, by sequence or size or relationship to each other. Furthermore, no limiting definitions are given in the specification. Thus, these limitations are very broad and encompass any number of nucleotides and /or sequence. Furthermore, the use of the word “comprising” indicates that the labels, universal primer, and biotin-tagged oligonucleotides could be directly or indirectly; i.e., via another moiety or bridge, ligated or even hybridized to each other or to other moieties.
The label in claim 1 and 21 is interpreted as: An oligonucleotide comprising two portions (exemplified as 305 and 303 in Fig. 4), wherein:
one portion comprises different sequences (m) that are connected to a second portion. In the absence of a specific recitation for the manner in which a label comprising different sequences and a universal primer are connected, if at all, the different sequences and universal primer that comprise the label could be comprised together by any means possible, for e.g., ligated end-to-end or hybridized via a complementary domain to each other or via a linker moiety.
the second portion comprises a universal primer. In the absence of a limiting definition for universal primer, the universal primer is being interpreted as a sequence of nucleotides that is common to all labels.
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[AltContent: textbox (5’ universal primer)][AltContent: textbox (3’ cohesive DNA end)][AltContent: textbox (LABEL)]The universal primer is at the 5’ end of the label that it is comprised within. Therefore, the cohesive DNA end may be within this end and binds in turn to the target. For prior art purposes, one embodiment of the orientation is in the figure below.
Since the label is recited in line 5 of claims 1 and 21 as comprising a cohesive end, it is understood that only one end of the label is capable of being ligated to another nucleotide; i.e., the label does not form a circular structure when ligated to another nucleotide.
Accordingly, claims 1 and 21 are interpreted as: A composition/kit, comprising:
fragmented DNA comprising at least four distinct target molecules comprising SNPs
two sets of oligonucleotides that each “connect” with at least one target nucleic acid sequence to be detected, wherein:
one set (recited as labels), comprises a cohesive DNA end that may ligate with fragmented target sequences,
and the other set (recited as at least four biotin-tagged oligonucleotides) comprises biotin-tagged sequences each with at least one nucleotide complementary to at least one of four distinct target molecules (PIK3R1, MYC, CCND2, or CDKN2A); i.e., this set may hybridize with at least one target.
two or more target DNA-modifying enzymes (to generate ends that are compatible for ligation with said cohesive end), wherein the fragmented DNA comprises four or more distinct target molecules comprising SNP(s), wherein the target DNA-modifying enzymes are exonuclease and/or polymerases or kinases; streptavidin magnetic beads; and one or more ligases.
Withdrawn Claim Rejections - 35 USC § 102
Response to Arguments
Applicants argue Re: Mirkin, on pg. 5:
claims 1 and 21 have been amended to recite, in part, "wherein a label comprises a cohesive DNA end and a 5' universal primer."
the Office Action does not allege that Mirkin discloses a label comprising a cohesive DNA end and a 5' universal primer.
This is persuasive, Mirkin in [0144] teach that the DNA barcode can be made into a universal probe i.e., reads on universal primer and regarding the DNA barcode in [0025] state: [T]he detection probe comprises (i) one or more specific binding complements to the second binding site of a specific target analyte; i.e., reads on cohesive end.
However, with respect to the amendment, the 5' universal primer, Mirkin teach in [0139] and [0152], oligonucleotides have moieties covalently bound to their 5' or 3' ends so as to allow for the oligonucleotides to be used to bind to a variety of nanoparticles. Thus, the universal primer may be either at 5’ or 3’ end of the label. Mirkin does not specifically require a 5’ universal primer. Therefore, the §102 rejection in view of Mirkin has been withdrawn. Instead, in view of amendment, a §103 rejection in view of Mirkin and Rittie is made in this office action.
Applicants argue Re: Brenner, on pgs. 5 onwards:
On pgs 6-7, Applicants repeat pertinent Office Action paragraphs.
On pg. 7, Applicants state, claims 1 and 21 have been amended to recite, in part, "wherein a label comprises a cohesive DNA end and a 5' universal primer."
On pg 8, first para, Applicants repeat pertinent Office Action paragraphs citing Brenner.
On pg. 8, last para, Applicants state:
i) the cited disclosure of Brenner does not teach or suggest label comprising a cohesive DNA end and a 5' universal primer. Brenner paragraph [0039] describes a stepwise tagging and processing workflow in which already adapted fragments are melted, primer (210) is annealed, and the primer is extended by DNA polymerase. Thus, even assuming arguendo that primer (210) is considered a "universal primer," Brenner still teaches a separate primer used in an annealing/extension step, not a label that itself comprises the claimed structure. The Office Action alternatively maps Brenner's adaptor "words" to the claimed different label sequences and maps Brenner's RE sequences/spacer to the claimed universal primer, but Brenner does not thereby disclose a label comprising both a cohesive DNA end and a 5' universal primer.
ii) Applicant notes that, as reflected in FIG. 2A, Brenner employs a biotinylated primer (210). By contrast, claim 1 separately requires four or more biotin-tagged oligonucleotides containing sequences complementary to the target molecules, together with streptavidin magnetic beads. Thus, the claims require a separate class of biotin-tagged target-complementary oligonucleotides serving a different function from Brenner's biotin-associated components.
iii) The Office Action does not explain why a skilled artisan would have modified Brenner to use both Brenner's biotinylated primer (210) and, in addition, a separate set of biotin-tagged target-complementary oligonucleotides as claimed. Nor does it explain how such a modification would be implemented without materially changing Brenner's disclosed workflow.
7. On pg 10, Applicants reproduce Fig. 2A from Brenner.
The argument in #6 above is persuasive.
Brenner teach two sets of tagged oligonucleotides are prepared:
One set of tagged oligonucleotide is an adaptor. This is seen in the figure reproduced by Applicant. The other set is referred to as tag complements [0040 - 0041] or anti-tags [0051] which is equivalent to four or more biotin tagged oligonucleotides. However, as applicants have reasoned, Brenner already recites biotin-tagged oligonucleotides as being part of the label. No reason or motivation to take these biotin tagged oligonucleotides out from the label in order to generate a separate set of oligonucleotides can be gleaned. Therefore, the §102 rejection in view of Brenner has been withdrawn.
New 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 pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter 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 pre-AIA 35 U.S.C. 103(a) 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 under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
These are new rejections necessitated by amendment.
I. Claim(s) 1-2, 4, 6 – 10, 12 – 18, 20-22, and 24-25 is/are rejected under pre-AIA 35 U.S.C. 102(a) as being anticipated by Mirkin (US 2005/0037397 A1, IDS dated 12/10/2025), and evidenced by Nannya (Cancer Res 2005;65: (14) July 15, 2005) in view of Rittie (J. Cell Commun. Signal. (2008) 2:25–45).
Regarding claims 1 and 21, Mirkin had taught a screening method for detecting the presence or absence of one or more target analytes, e.g., nucleic acids ([0003], Example 10, [0372]). The method utilizes oligonucleotides as biochemical barcodes for detecting multiple analytes in one solution [0007], Fig. 16.
A specific method comprising putting together the following:
DNA sequences comprising a gene sequence and two DNA positive controls [0372] from DNA fragments ([0253], [0290], [0308], claim 44);
two sets of nanoparticle-attached probes that each connect with at least one target nucleic acid sequence to be detected, wherein each probe comprises two parts, wherein one part is a specific binding complement to a specific target analyte (nucleic acid fragment)
One set is a detection probe. E.g. see recitation [0021] providing one or more types of detection probes, each type of detection probe comprising a nanoparticle having oligonucleotides bound thereto, one or more specific binding complements to a second binding site of the specific target analyte, and one or more DNA barcodes that serve as a marker for the particular target analyte, wherein at least a portion of a sequence of the DNA barcodes is hybridized to at least some of the oligonucleotides bound to the nanoparticles
The other set is a capture probe. E.g. see recitation [0020]: providing one or more types of capture probes bound to a substrate, each type of capture probe comprising a specific binding complement to a first binding site of a specific target analyte.
Mirkin further taught the following about the detection probe:
[0025]: [T]he detection probe comprises (i) one or more specific binding complements to the second binding site of a specific target analyte, (ii) at least one type of oligonucleotides bound to the nanoparticle, and a DNA barcode having a predetermined sequence that is complementary to at least a portion of at least one type of oligonucleotides, the DNA barcode bound to each type of detection probe serving as a marker for a specific target analyte; [0029]: the DNA barcode is amplified by PCR; [0052]: [T]he nanoparticles are metal nanoparticles such as gold nanoparticles or semiconductor nanoparticles; [0116]: [T]he DNA barcode is a an oligonucleotide with a predefined sequence, is also called the reporter probe, and may be further labelled for e.g., with biotin; the DNA barcode can be made into a universal probe as taught in: [0144] These universal probes can be … "tuned" to various single target nucleic acid sequences, by simply substituting or interchanging the target recognition oligonucleotides such that the second portion comprises complementary sequence to the target nucleic acid of interest. Similarly, if multiple target nucleic acid sequences are to be assayed in a single test solution, the reporter oligonucleotides can comprise a sequence that is specific for each target nucleic acid. Thus, detection of the reporter oligonucleotide of known and specific sequence, would indicate the presence of the particular target nucleic acid in the test solution.
Mirkin further taught the following about the capture probe: [0030]: [T]he capture probe is bound to a magnetic substrate such as a magnetic particle.
Mirkin taught the following about the enzymes used in the method: [0150]: Methods of making oligonucleotides of a predetermined sequence are well known. They further cite well-known texts in the field.
Having taught such method, Mirkin inherently taught a composition comprising instant limitations. Specifically, in Mirkin’s method, Mirkin’s detection probe (instant label) comprising i. binding complements to the second binding site of a specific target analyte and ii. barcode/universal probe read on instant label with i. cohesive ends and ii. a universal primer respectively, and the capture probe reads on instant biotin-tagged oligonucleotides.
While Mirkin does not make mention of the four or more distinct target molecules: PIK3R1, MYC, CCND2, or CDKN2A, Nannya evidences the presence of these four SNP containing target molecules in genomic DNA from one sample. See Nannya Table 1, as well as incorporated by reference in instant application.
Amendment: With respect to the amendment in claim 1 and 21, the 5' universal primer, Mirkin teach in [0139] and [0152], oligonucleotides have moieties covalently bound to their 5' or 3' ends so as to allow for the oligonucleotides to be used to bind to a variety of nanoparticles. Thus, the universal probe of Mirkin’s Fig. 16 for e.g., could be bound via its 3’ end or bound via its 5’end to a nanoparticle. See also claim interpretation.
Regarding claims 6 - 7 and 25, Mirkin had taught that the composition in their method requires labels to be in excess of fragments to be tagged. See recitation below providing an explanation.
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Regarding claims 8 - 9, Mirkin had taught in their examples, label sequences are up to 12mers (Example 10:… oligonucleotide-modified gold NP probes (5'-TCT CAA CTC GTA GCT-A10-SH-3 '-Au; SEQ ID NO:17); Example 6:…evidenced by the lack of signal from the control spots with noncomplementary capture DNA (5'SH-C6-A10-GGCAGCTCGTGGTGA-3', SEQ ID NO:13), which reads on the recitation of at least 6 nucleotides in length and 6-15 nucleotides in length.
Regarding claim 10, Mirkin had taught that the target comprises a plurality of target molecules (substrate comprises a plurality of types of oligonucleotides, claims 73-74). Such teachings read on instant recitation of plurality of first target molecules and plurality of second target molecules.
Regarding claims 15 - 17, Mirkin had taught their method requires that the DNA to be detected comes from a sample (claim 47; biomolecules, in a sample, abstract; A method for detecting for the presence or absence of one or more target analytes in a sample, claim 6).
Finally, Mirkin had taught wherein the composition comprises enzymes for PCR and oligonucleotide modification [0150]. Working examples utilize polymerases for amplification, for e.g., [0360] and that use of enzymes and methods for polymerization were well-known in the art.
Mirkin had not taught i. the universal primer is specifically at the 5’ end of the label (claims 1 and 21), ii. method of ligation in the creation of a label comprised of a label sequence and universal primer that would require kinases and ligases (claims 1 and 21), iii. the specific polymerases, and iii. do not require reverse transcription to require a reverse transcriptase, or any specific enzymes recited in instant dependent claims 2, 4, 12-14, 18-20, 22, and 24.
However, before the time of the effective filing date, the skilled artisan was aware of various choices of enzymes for PCR and oligonucleotide modification as reviewed in the art of Rittie. Rittie had provided a useful guide to enzymes used in molecular biology. Rittie’s Table 1 describes various polymerases, Table 3 describes various ligases, and Table 4 describes various kinases, including recited polymerases, ligases and kinases, with advantages and disadvantages of each. Specifically, Rittie had taught several advantages to having a universal primer at the 5’-end such as being able to use a terminal deoxynucleotidyl transferase (TdT), which catalyzes the addition of a homopolymer tail to 3′-OH ends of DNA, in a template-independent manner. Other advantages for incorporation of various enzymes into the composition of Mirkin that are taught by Rittie are: i. The 5′→3′ exonuclease activity of Pol I is utilized in vitro for nick-translation (i.e. tagging technique in which some of the nucleotides of a DNA sequence are replaced with labeled analogues), ii. Klenow fragment contains the 5′→3′ polymerase and 3′→5′ exonuclease (proofreading) activities of DNA Pol I, iii. Terminal deoxynucleotidyl transferase (TdT), catalyzes the addition of a homopolymer tail to 3′-OH ends of DNA, in a template-independent manner, iv. reverse transcriptase (RT) enable single stranded DNA to be synthesized from an RNA template, v. T4-DNA Ligase allows for blunt and cohesive ends in duplex DNA, RNA or DNA/RNA hybrids to be connected, and vi. T4 Polynucleotide Kinase used in nucleic acid labeling as it allows for transfer of a phosphate group from ATP to 5′-OH terminus of a nucleic acid at neutral pH. See Rittie, pgs. 27 - 34.
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date to have a universal primer at the 5’-end so as to be able to use a terminal deoxynucleotidyl transferase (TdT), which catalyzes the addition of a homopolymer tail to 3′-OH ends of DNA, in a template-independent manner. Also one would be motivated to add to the composition used in the method of Mirkin specific polymerases as taught by Rittie. One would have been motivated to make such a modification to perform PCR and oligonucleotide modification in order to receive the expected benefit of optimal performance as taught by Rittie. Further, one would have incorporated kinases and ligases into the composition to have the choice of ligating a label sequence with a universal primer in the creation of a label. One of ordinary skill in the art would have a reasonable expectation of success in doing so since both Mirkin and Rittie teach methods for analysis of DNA. The combination of prior art elements according to known methods to yield predictable results supports a conclusion of obviousness. See MPEP 2143(I) A.
Thus, Mirkin in view of Rittie makes obvious instant claims 1-2, 4, 6 – 10, 12 – 18, 20-22, and 24-25.
II. Claims 3, 11, and 23 is/are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Mirkin (US 2005/0037397 A1, IDS dated 12/10/2025) and evidenced by Nannya (Cancer Res 2005;65: (14) July 15, 2005) in view of Rittie (J. Cell Commun. Signal. (2008) 2:25–45) as applied to claims 1-2, 4, 6 – 10, 12 – 18, 20-22, and 24-25 above, and further in view of Lockhart (US 6,361,947 B1).
The teachings of Mirkin and Rittie have been discussed in the rejection for claims 1- and 21 above and apply.
Regarding claims 3 and 23, Mirkin had taught wherein the target DNA is fragmented, [0290].
Neither Mirkin nor Rittie had taught fragmented DNA is sheared as recited in instant claim 3.
However, before the time of the effective filing date, the skilled artisan was aware of various means for fragmenting DNA for PCR, labelling, and oligonucleotide modifications for further analysis, for e.g., as taught in the art of Lockhart. Lockhart had provided methods of sample preparation and analysis involving reproducibly reducing the complexity of a nucleic sample (abstract). Lockhart had taught physical fragmentation methods may involve subjecting the DNA to a high shear rate. Further, Lockhart had taught how one may achieve such shearing (column 9, 1st para).
Regarding claim 11, Mirkin had taught the recitation of claim 10; i.e., a plurality of target molecules ([00891]: the substrate comprises a plurality of types of oligonucleotides), but neither Mirkin nor Rittie had specifically taught ratios of tags to target DNA as recited in claim 11.
Lockhart had taught their method requires an excess of oligonucleotides to target DNA (biotin-tagged oligonucleotides containing sequences complementary to the regions of desired SNPs were mixed with target DNA in a 1000:1 ratio. (Alternatively, a 10:1, 20:1, 50:1, 250:1 or any other ratio could have been chosen), column 19, 5th para titled SNP Discovery-Method 4). Thus, it is implied that Lockhart had suggested the ratio of the greater of n1 and n2 to m is smaller than 0.2, as recited in claim 11.
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date to modify the target DNA in the composition used in the method of Mirkin and Rittie with sheared DNA as taught by Lockhart. One would have been motivated to make such a modification in order to receive the expected benefit of low complexity DNA which in turn would enable more efficient PCR and oligonucleotide modification, as taught by Lockhart. Further, one of skill in the art knows, the reason why PCR works is because initially there is a large excess of primer over target DNA, so the hybridizations take place very rapidly. Therefore, one of skill in the art would be motivated to use excess of labels over DNA to achieve higher efficiency of hybridization or ligation. One of ordinary skill in the art would have a reasonable expectation of success since Mirkin, Rittie, and Lockhart teach methods for analysis of DNA. The combination of prior art elements according to known methods to yield predictable results supports a conclusion of obviousness. See MPEP 2143(I) A.
Thus, Mirkin and Rittie in view of Lockhart make obvious instant claims 3, 11, and 23.
Therefore the invention as a whole would have been prima facie obvious to one ordinary skill in the art before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains.
Response to Arguments
Applicant’s arguments with respect to claim(s) 2-20 and 22-25 rejected under § 103 have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Maintained 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.
The rejections below are maintained for reasons of record set forth in the office action of 9-10-2025, repeated in 1/21/2026, and reiterated below.
Claims 1-4 and 6-25 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 26 - 30, 39 – 67, 73 – 118, 124 - 138 of U.S. Patent No.8,835,358 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because they are both drawn to elements that are used in a method of detecting nucleic acid sequences by attaching diverse sequences (labels) to one end of the sequences to be detected, thus overlapping in scope.
Claims of the present application are drawn to a composition that comprises diverse label sequences and enzymes for attaching these to a plurality of occurrences of at least one target sequence, wherein the number of labels is m, and number of occurrences of first and second target molecules is n1 and n2 respectively, and the ratio of the greater of n1 and n2 to m is smaller than 0.2.
Claim 26 of the ‘358 patent is drawn to a method that comprises attaching a label from a set of diverse labels to each occurrence of a first target molecule and detecting each molecule by detecting each label present on the new molecule and counting the number of new molecules, wherein the number of label is m, and the number of first molecule is n. Claim 27 from the ‘358 patent further recites that the ratio of m to n is greater than 50.
It would have been obvious to an ordinary skilled in the art to use the claimed composition of the present application in the method of the ‘358 patent because their method requires the attaching of a label to a number of occurrences of a target molecule and counting the new labeled molecules. The ratio of m to n is greater than 50 claimed in claim 27 of the ‘358 patent is same as the ratio of n to m smaller than 0.02 claimed in claim 11 of the present application.
Although the method in claim 26 of the ‘358 patent does not recite:
four or more biotin-tagged oligonucleotides containing sequences each complementary to at least one of the four or more distinct target molecules wherein at least one of the four or more distinct target nucleic acid molecules is PIK3R1, MYC, CCND2, or CDKN2A; it would have been obvious to an ordinary skilled in the art that multiple targets may be present in the sample for practice the same method, this is evidenced by claims 42 and 43 of the ‘358 patent, wherein the method recites additional target molecules are included in the sample.
Therefore, instant claims 1 – 20 would have been obvious to use in the method as claimed in claims 26 - 30, 39 – 67, 73 – 118, 124 - 138 of the ‘358 patent;
Any additional limitations of the reference application claims are encompassed by the open claim language “comprises” found in the instant claims.
Claims 1-4 and 6-25 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 123, 145 – 155, 157 - 161, 163 – 164, and 172 of U.S. Patent No.9315857 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because they are both drawn to elements that are used in a method of detecting nucleic acid sequences by attaching diverse sequences (labels) to one end of the sequences to be detected, thus overlapping in scope.
Claims of the present application are drawn to a composition that comprises diverse label sequences and enzymes for attaching these to a plurality of occurrences of at least one target sequence, wherein the number of labels is m, and number of occurrences of first and second target molecules is n1 and n2 respectively, and the ratio of the greater of n1 and n2 to m is smaller than 0.2.
Claim 123 of the ‘857 patent is drawn to a method that comprises attaching a label from a set of diverse labels to multiple copies of target molecules and detecting each molecule by detecting each label present on the new molecule and counting the number of new molecules, wherein the target is fragmented DNA.
It would have been obvious to an ordinary skilled in the art to use the claimed composition of the present application in the method of the ‘857 patent because their method requires the attaching of a label to a number of occurrences of a target molecule and counting the new labeled molecules.
Although the method in claim 123 of the ‘857 patent does not recite:
four or more biotin-tagged oligonucleotides containing sequences each complementary to at least one of the four or more distinct target molecules wherein at least one of the four or more distinct target nucleic acid molecules is PIK3R1, MYC, CCND2, or CDKN2A; it would have been obvious to an ordinary skilled in the art that multiple targets may be present in the sample for practice the same method, this is evidenced by [0238] of the disclosure that describes preparation of the target which is fragmented DNA from genomic DNA, thus encompassing any target molecules are included in the sample.
Therefore, instant claims 1 – 20 would have been obvious to use in the method as claimed in claims 123, 145 – 155, 157 - 161, 163 – 164, and 172 of the ‘857 patent;
Any additional limitations of the reference application claims are encompassed by the open claim language “comprises” found in the instant claims.
Claims 1-4 and 6-25 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 31 – 66, and 68 - 71 of U.S. Patent No.9816137 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because they are both drawn to elements that are used in a method of detecting nucleic acid sequences by attaching diverse sequences (labels) to one end of the sequences to be detected, thus overlapping in scope.
Claims of the present application are drawn to a composition that comprises diverse label sequences and enzymes for attaching these to a plurality of occurrences of at least one target sequence, wherein the number of labels is m, and number of occurrences of first and second target molecules is n1 and n2 respectively, and the ratio of the greater of n1 and n2 to m is smaller than 0.2.
Claim 31 of the ‘137 patent is drawn to a method that comprises attaching a primer wherein the primer comprises a different variable region to multiple copies of nucleic acids, amplifying, and detecting each labelled molecule by detecting each label present on the new molecule and counting the number of new molecules. Dependent claims require the target to be genomic DNA, and the label further comprising a universal primer.
It would have been obvious to an ordinary skilled in the art to use the claimed composition of the present application in the method of the ‘137 patent because their method requires the attaching of a label to a number of occurrences of a target molecule and counting the new labeled molecules; i.e., the components of instant claim.
Although the method in claim 31 of the ‘137 patent does not recite:
four or more biotin-tagged oligonucleotides containing sequences each complementary to at least one of the four or more distinct target molecules wherein at least one of the four or more distinct target nucleic acid molecules is PIK3R1, MYC, CCND2, or CDKN2A; it would have been obvious to an ordinary skilled in the art that multiple targets may be present in the sample for practice the same method, this is evidenced by claim 55 of the reference application that recites the target which is genomic DNA, thus encompassing any target molecules are included in the sample.
Therefore, instant claims 1 – 20 would have been obvious to use in the method as claimed in claims 31 – 66, and 68 - 71 of the ‘137 patent;
Any additional limitations of the reference application claims are encompassed by the open claim language “comprises” found in the instant claims.
Claims 1-4 and 6-25 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 7 - 15, 17, 19 – 20, 26 - 31 of U.S. Patent No.9,290,809 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because they are both drawn to elements of a composition that are used in a method of detecting nucleic acid sequences by attaching diverse sequences (labels) to one end of the sequences to be detected, thus overlapping in scope.
Claims of the present application are drawn to a composition that comprises diverse label sequences and enzymes for attaching these to a plurality of occurrences of at least one target sequence, wherein the number of labels is m, and number of occurrences of first and second target molecules is n1 and n2 respectively, and the ratio of the greater of n1 and n2 to m is smaller than 0.2.
Claim 1 of the ‘809 patent is also drawn to a composition used in a method that comprises attaching a label from a set of diverse labels to each occurrence of a first target molecule and detecting each molecule by detecting each label present on the new molecule and counting the number of new molecules, wherein the number of label is m. Dependent claims further recite the number of first molecule is n. Claim 15 from the ‘809 patent further recites that the ratio of m to n is greater than 5.
It would have been obvious to an ordinary skilled in the art to utilize the claimed composition of the present application in place of the claimed composition of the reference application in a method that requires the attaching of a label to a number of occurrences of a target molecule and counting the new labeled molecules. The ratio of m to n is greater than 5 claimed in claim 15 of the ‘809 patent is same as the ratio of n to m smaller than 0.2 claimed in claim 11 of the present application.
Although the composition of the ‘809 patent does not recite:
four or more biotin-tagged oligonucleotides containing sequences each complementary to at least one of the four or more distinct target molecules wherein at least one of the four or more distinct target nucleic acid molecules is PIK3R1, MYC, CCND2, or CDKN2A; it would have been obvious to an ordinary skilled in the art that multiple targets may be present in the sample for practice the method requiring the composition, this is evidenced by claim 29 of the ‘809 patent, wherein the composition requires “two or more different target sequences”.
Therefore, instant claims 1 – 25 are obvious over claims 1, 7 - 15, 17, 19 – 20, 26 - 31 of the ‘809 patent;
Any additional limitations of the reference application claims are encompassed by the open claim language “comprises” found in the instant claims.
Claims 1-4 and 6-25 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 31 – 58, 60, 63 - 67 of U.S. Patent No.10,619,203. Although the claims at issue are not identical, they are not patentably distinct from each other because they are both drawn to elements that are used in a method of detecting nucleic acid sequences by attaching diverse sequences (labels) to one end of the sequences to be detected, thus overlapping in scope.
Claims of the present application are drawn to a composition that comprises diverse label sequences and enzymes for attaching these to a plurality of occurrences of at least one target sequence, wherein the number of labels is m, and number of occurrences of first and second target molecules is n1 and n2 respectively, and the ratio of the greater of n1 and n2 to m is smaller than 0.2.
Claims 31 and 34 of the ‘203 patent are drawn to a method of randomly attaching label sequences from a set of m label sequences to first target molecule that comprises a first allele at a first polymorphic site and a second target molecules that comprises a second allele at a second polymorphic site in a sample, and detecting the new molecule having label attached to the target sequences by detecting the label sequence, wherein the number of label is m, and number of occurrences of first and second target molecule is n1 and n2 respectively, and the ratio of the greater of n1 and n2 to m is smaller than 0.2.
It would have been obvious to an ordinary skilled in the art that the claimed method of claims 1 and 34 of the ‘203 patent utilizes the composition of instant claims 1 - 25 (of the present application). The ‘203 patent’s recitation of the target molecule to comprising a first allele at a first polymorphic site and second target molecules comprises a second allele at a second polymorphic site encompasses instant claim’s recitation of:
four or more biotin-tagged oligonucleotides containing sequences each complementary to at least one of the four or more distinct target molecules wherein at least one of the four or more distinct target nucleic acid molecules is PIK3R1, MYC, CCND2, or CDKN2A.
It would have been obvious to an ordinary skilled in the art that multiple targets may be present in the sample for practice of the method and that these targets could be the same as recited in instant claims.
Therefore, claims 1 - 25 would have been obvious to use in the method as claimed in claims 31 and 34 of the ‘203 patent.
Any additional limitations of the reference application claims are encompassed by the open claim language “comprises” found in the instant claims.
Claims 1-4 and 6-25 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 31-50 of U.S. Patent No. 10,047,394. Although the claims at issue are not identical, they are not patentably distinct from each other because they are both drawn to elements that are used in a method of detecting nucleic acid sequences by attaching diverse sequences (labels) to one end of the sequences to be detected, thus overlapping in scope.
Claims of the present application are drawn to a composition that comprises diverse label sequences and enzymes for attaching these to a plurality of occurrences of at least one target sequence, wherein the number of labels is m, and number of occurrences of first and second target molecules is n1 and n2 respectively, and the ratio of the greater of n1 and n2 to m is smaller than 0.2.
Claim 31 of the ‘394 patent is drawn to a method of randomly attaching label sequences from a set of m label sequences to first target molecule and a second target molecules in a sample, and detecting the new molecule having label attached to the target sequences by detecting the label sequence, wherein the number of label is m, and number of occurrences of first and second target molecule is n1 and n2 respectively, and the ratio of the greater of n1 and n2 to m is smaller than 0.2, and wherein more than 90% of the new first and second molecules have a label that is different from the labels on the other new first molecules and new second molecules.
It would have been obvious to an ordinary skilled in the art that the claimed method of claim 31 of the ‘394 patent utilizes the composition of instant claims 1 - 25. As such, the composition recited in Claims 1 - 25 of the present application are not patentably distinct from a composition needed to perform the method of claim 31 from the ‘394 patent.
Although the method in claim 31 of the ‘394 patent does not recite:
four or more biotin-tagged oligonucleotides containing sequences each complementary to at least one of the four or more distinct target molecules wherein at least one of the four or more distinct target nucleic acid molecules is PIK3R1, MYC, CCND2, or CDKN2A; it would have been obvious to an ordinary skilled in the art that the first and second target molecules that are present in the sample for practice of the method; it would have been obvious to an ordinary skilled in the art looking at the disclosure of the ‘394 patent, wherein the method described in [0106] discloses that the method can simultaneously count copies of multiple target sequences, without specifically naming any target sequence.
Therefore, claims 1 - 25 would have been obvious to use in the method as claimed in claim 31 of the ‘394 patent.
Any additional limitations of the reference application claims are encompassed by the open claim language “comprises” found in the instant claims.
Claims 1-4 and 6-25 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of U.S. Patent No. 10,202,646. Although the claims at issue are not identical, they are not patentably distinct from each other because they are both drawn to elements that are used in a method of detecting nucleic acid sequences by attaching diverse sequences (labels) to one end of the sequences to be detected, thus overlapping in scope.
Claims of the present application are drawn to a composition that comprises diverse label sequences and enzymes for attaching these to a plurality of occurrences of at least one target sequence, wherein the number of labels is m, and number of occurrences of first and second target molecules is n1 and n2 respectively, and the ratio of the greater of n1 and n2 to m is smaller than 0.2.
Claim 1 of the ‘646 patent is drawn to a method of randomly attaching label sequences from a set of m label sequences to first target molecule and a second target molecules in a sample, and detecting the new molecule having label attached to the target sequences by detecting the label sequence, wherein the number of label is m, and number of occurrences of first and second target molecule is n1 and n2 respectively, and the ratio of the greater of n1 and n2 to m is smaller than 0.2, and wherein more than 90% of the new first and second molecules have a label that is different from the labels on the other new first molecules and new second molecules.
It would have been obvious to an ordinary skilled in the art that the claimed method of claim 1 of the ‘646 patent utilizes the composition of instant claims 1 - 25 of the present application. As such, the composition claimed in Claims 1 - 25 of the present application are not patentably distinct from the composition needed to practice the method of claim 1 from the ‘646 patent.
Although the method in claim 1 of the ‘646 patent does not recite:
four or more biotin-tagged oligonucleotides containing sequences each complementary to at least one of the four or more distinct target molecules wherein at least one of the four or more distinct target nucleic acid molecules is PIK3R1, MYC, CCND2, or CDKN2A; it would have been obvious to an ordinary skilled in the art that multiple targets may be present in the sample for practice the same method; it would have been obvious to an ordinary skilled in the art looking at the disclosure of the ‘646 patent, wherein the method described in [0013] discloses that the method can simultaneously count copies of multiple target sequences, without specifically naming any target sequence.
Therefore, claims 1 - 25 would have been obvious to use in the method as claimed in claim 1 of the ‘646 patent.
Any additional limitations of the reference application claims are encompassed by the open claim language “comprises” found in the instant claims.
Claims 1-4 and 6-25 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of U.S. Patent No. 10,392,661. Although the claims at issue are not identical, they are not patentably distinct from each other because they are both drawn to elements that are used in a method of detecting nucleic acid sequences by attaching diverse sequences (labels) to one end of the sequences to be detected, thus overlapping in scope.
Claims of the present application are drawn to a composition that comprises diverse label sequences and enzymes for attaching these to a plurality of occurrences of at least one target sequence, wherein the number of labels is m, and number of occurrences of first and second target molecules is n1 and n2 respectively, and the ratio of the greater of n1 and n2 to m is smaller than 0.2.
Claim 1 of the ‘661 patent is drawn to a method of randomly attaching label sequences from a set of m label sequences to first target molecule and a second target molecules in a sample, and detecting the new molecule having label attached to the target sequences by detecting the label sequence, wherein the number of label is m, and number of occurrences of first and second target molecule is n1 and n2 respectively, and the ratio of the greater of n1 and n2 to m is smaller than 0.2.
It would have been obvious to an ordinary skilled in the art that the claimed method of claim 1 of the ‘661 patent utilizes the composition of instant claims 1 - 25. As such, the composition claimed in claims 1 - 25 of the present application are not patentably distinct from the composition used in the method of claim 1 from the ‘661 patent.
Although the method in claim 1 of the ‘661 patent does not recite:
four or more biotin-tagged oligonucleotides containing sequences each complementary to at least one of the four or more distinct target molecules wherein at least one of the four or more distinct target nucleic acid molecules is PIK3R1, MYC, CCND2, or CDKN2A; it would have been obvious to an ordinary skilled in the art looking at the disclosure of the ‘661 patent, wherein the method described in [0013] discloses that the method can simultaneously count copies of multiple target sequences, without specifically naming any target sequence.
Therefore, claims 1 - 25 would have been obvious to use in the method as claimed in claim 1 of the ‘661 patent.
Any additional limitations of the reference application claims are encompassed by the open claim language “comprises” found in the instant claims.
Claims 1-4 and 6-25 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 31, 33 – 36, 38 - 67 of U.S. Patent No. 10,059,991. Although the claims at issue are not identical, they are not patentably distinct from each other because they are both drawn to elements that are used in a method of detecting nucleic acid sequences by attaching diverse sequences (labels) to one end of the sequences to be detected, thus overlapping in scope.
Claims of the present application are drawn to a composition that comprises diverse label sequences and enzymes for attaching these to a plurality of occurrences of at least one target sequence, wherein the number of labels is m, and number of occurrences of first and second target molecules is n1 and n2 respectively, and the ratio of the greater of n1 and n2 to m is smaller than 0.2.
Claim 31 of the ‘991 patent is drawn to a method of randomly attaching label sequences from a set of m label sequences to first target molecule and a second target molecules in a sample, amplifying the labeled first and second target molecule to create clonal population of the first and second molecule, and detecting the new molecule having label attached to the target sequences by detecting the label sequence, wherein the number of label is m, and number of occurrences of first and second target molecule is n1 and n2 respectively, and the ratio of the greater of n1 and n2 to m is smaller than 0.2, and wherein more than 90% of the new first and second molecules have a label that is different from the labels on the other new first molecules and new second molecules.
It would have been obvious to an ordinary skilled in the art that the claimed method of claim 31 of the ‘991 patent utilizes the composition of instant claims 1 - 25 of the present application. As such, the method claimed in Claims 1 - 25 of the present application is not patentably distinct from the method of claim 1 from the ‘991 patent.
Although the method in claim 31 of the ‘991 patent does not recite:
four or more biotin-tagged oligonucleotides containing sequences each complementary to at least one of the four or more distinct target molecules wherein at least one of the four or more distinct target nucleic acid molecules is PIK3R1, MYC, CCND2, or CDKN2A; it would have been obvious to an ordinary skilled in the art looking at the disclosure of the ‘991 patent, wherein the method described in [0013] discloses that the method can simultaneously count copies of multiple target sequences, without specifically naming any target sequence. Therefore, claims 1 - 25 would have been obvious to use in the method as claimed in claim 1 of the ‘991 patent.
Any additional limitations of the reference application claims are encompassed by the open claim language “comprises” found in the instant claims.
Claims 1-4 and 6-25 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 31-58 of U.S. Patent No. 12,060,607 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because they are both drawn to elements that are used in a method of detecting nucleic acid sequences by attaching diverse sequences (labels) to one end of the sequences to be detected, thus overlapping in scope.
Claims of the present application are drawn to a composition that comprises diverse label sequences and enzymes for attaching these to a plurality of occurrences of at least one target sequence, wherein the number of labels is m, and number of occurrences of first and second target molecules is n1 and n2 respectively, and the ratio of the greater of n1 and n2 to m is smaller than 0.2.
Claim 31 of the ‘607 patent is drawn to a method that comprises the steps of randomly attaching label sequences from a set of m label sequences to first target molecule and a second target molecules in a sample, and detecting the new molecule having label attached to the target sequences by detecting the label sequence, wherein the number of label is m, and number of occurrences of first and second target molecule is n1 and n2 respectively, and the ratio of the greater of n1 and n2 to m is smaller than 0.2.
It would have been obvious to an ordinary skilled in the art to utilize the composition of instant claims 1 - 25 in the claimed method of claims of the ‘607 patent. As such, the method claimed in Claims 1 - 25 of the present application is not patentably distinct from the method of claim 1 from the ‘607 patent.
Although the method in claim 31 of the ‘607 patent does not recite:
four or more biotin-tagged oligonucleotides containing sequences each complementary to at least one of the four or more distinct target molecules wherein at least one of the four or more distinct target nucleic acid molecules is PIK3R1, MYC, CCND2, or CDKN2A; it would have been obvious to an ordinary skilled in the art that multiple targets may be present in the sample for practice the same method; it would have been obvious to an ordinary skilled in the art looking at the disclosure of the ‘607 patent, wherein the method described in [0013] discloses that the method can simultaneously count copies of multiple target sequences, without specifically naming any target sequence.
Therefore, claims 1 - 25 would have been obvious to use in the method as claimed in claim 31 of the ‘607 patent.
Any additional limitations of the reference application claims are encompassed by the open claim language “comprises” found in the instant claims.
Claims 1-4 and 6-25 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-30 and 39 of Patent No. 11993814 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because they are both drawn to elements that are used in a method of detecting nucleic acid sequences by attaching diverse sequences (labels) to one end of the sequences to be detected, thus overlapping in scope.
Claims of the present application are drawn to a composition that comprises diverse label sequences and enzymes for attaching these to a plurality of occurrences of at least one target sequence, wherein the number of labels is m, and number of occurrences of first and second target molecules is n1 and n2 respectively, and the ratio of the greater of n1 and n2 to m is smaller than 0.2.
Claims 1 and 39 of the ‘814 patent are drawn to a method that comprises the steps of randomly attaching label sequences from a set of m label sequences to first target molecule and a second target molecules in a sample, and detecting the new molecule having label attached to the target sequences by detecting the label sequence, wherein the number of label is m, and number of occurrences of first and second target molecule is n1 and n2 respectively, and the ratio of the greater of n1 and n2 to m is smaller than 0.2.
It would have been obvious to an ordinary skilled in the art to utilize the composition of instant claims 1 - 25 in the claimed method of claims 1 and 39 of the ‘814 patent. As such, the composition claimed in Claims 1 - 25 of the present application is not patentably distinct from the method of claim 1 from the ‘814 patent.
Although the method in claims 1 and 39 of the ‘814 patent does not recite:
four or more biotin-tagged oligonucleotides containing sequences each complementary to at least one of the four or more distinct target molecules wherein at least one of the four or more distinct target nucleic acid molecules is PIK3R1, MYC, CCND2, or CDKN2A; it would have been obvious to an ordinary skilled in the art that multiple targets may be present in the sample for practice the same method; it would have been obvious to an ordinary skilled in the art looking at the disclosure of the ‘814 patent, wherein the method described in [0013] discloses that the method can simultaneously count copies of multiple target sequences, without specifically naming any target sequence.
Therefore, claims 1 - 25 would have been obvious to use in the method as claimed in claim 1 and 39 of the ‘814 patent.
Any additional limitations of the reference application claims are encompassed by the open claim language “comprises” found in the instant claims.
Claims 1-4 and 6-25 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 31-53 of Patent No. 11,970,737 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because they are both drawn to elements that are used in a method of detecting nucleic acid sequences by attaching diverse sequences (labels) to one end of the sequences to be detected, thus overlapping in scope.
Claims of the present application are drawn to a composition that comprises diverse label sequences and enzymes for attaching these to a plurality of occurrences of at least one target sequence, wherein the number of labels is m, and number of occurrences of first and second target molecules is n1 and n2 respectively, and the ratio of the greater of n1 and n2 to m is smaller than 0.2.
Claim 31 of the ‘737 patent is drawn to a method that comprises the steps of randomly attaching label sequences from a set of m label sequences to first target molecule and a second target molecules in a sample, and detecting the new molecule having label attached to the target sequences by detecting the label sequence, wherein the number of label is m, and number of occurrences of first and second target molecule is n1 and n2 respectively, and the ratio of the greater of n1 and n2 to m is smaller than 0.2.
It would have been obvious to an ordinary skilled in the art to utilize the composition of instant claims 1 - 25 in the claimed method of claim 31 of the ‘737 patent because the reference application requires the components of Claims 1 - 25 of the present application except the patent does not recite:
four or more biotin-tagged oligonucleotides containing sequences each complementary to at least one of the four or more distinct target molecules wherein at least one of the four or more distinct target nucleic acid molecules is PIK3R1, MYC, CCND2, or CDKN2A; it would have been obvious to an ordinary skilled in the art that multiple targets may be present in the sample for practice the same method,; it would have been obvious to an ordinary skilled in the art looking at the disclosure of the ‘737 patent, wherein the method described in [0013] discloses that the method can simultaneously count copies of multiple target sequences, without specifically naming any target sequence. Therefore, the inclusion of this wherein clause does not make change to the steps of method claimed in claim 1 of reference application. As such, the method claimed in Claims 1 - 25 of the present application is not patentably distinct from the method of claim 31 from the ‘737 patent.
Therefore, claims 1 - 25 would have been obvious to use in the method as claimed in claim 31 of the ‘737 patent.
Any additional limitations of the reference application claims are encompassed by the open claim language “comprises” found in the instant claims.
Claims 1-4 and 6-25 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 23 - 42 of reference application No. 18771886 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because they are both drawn to elements that are used in a method of detecting nucleic acid sequences by attaching diverse sequences (labels) to one end of the sequences to be detected, thus overlapping in scope.
Claims of the present application are drawn to a composition that comprises diverse label sequences and enzymes for attaching these to a plurality of occurrences of at least one target sequence, wherein the number of labels is m, and number of occurrences of first and second target molecules is n1 and n2 respectively, and the ratio of the greater of n1 and n2 to m is smaller than 0.2.
Claim 23 of the ‘886 reference application is drawn to a method that comprises the steps of randomly attaching label sequences from a set of m label sequences to first target molecule and a second target molecules in a sample, and detecting the new molecule having label attached to the target sequences by detecting the label sequence, wherein the number of label is m, and number of occurrences of first and second target molecule is n1 and n2 respectively, and the ratio of the greater of n1 and n2 to m is smaller than 0.2.
It would have been obvious to an ordinary skilled in the art to utilize the composition of instant claims 1 - 25 in the claimed method of claim 23 of the ‘886 reference application because the reference application requires the components of Claims 1 - 25 of the present application except the ‘886 reference application does not recite:
four or more biotin-tagged oligonucleotides containing sequences each complementary to at least one of the four or more distinct target molecules wherein at least one of the four or more distinct target nucleic acid molecules is PIK3R1, MYC, CCND2, or CDKN2A; it would have been obvious to an ordinary skilled in the art that multiple targets may be present in the sample for practice the same method; it would have been obvious to an ordinary skilled in the art looking at the disclosure of the ‘886 reference application, wherein the method described in [0013] discloses that the method can simultaneously count copies of multiple target sequences, without specifically naming any target sequence. As such, the composition claimed in Claims 1 - 25 of the present application are not patentably distinct from the method of claim 23 from the ‘870 reference application.
Therefore, claims 1 - 25 would have been obvious to use in the method as claimed in claim 23 of the ‘886 reference application.
Any additional limitations of the reference application claims are encompassed by the open claim language “comprises” found in the instant claims.
Claims 1-4 and 6-25 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 39-58 of Application No. 18/643,870 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because they are both drawn to elements that are used in a method of detecting nucleic acid sequences by attaching diverse sequences (labels) to one end of the sequences to be detected, thus overlapping in scope.
Claims of the present application are drawn to a composition that comprises diverse label sequences and enzymes for attaching these to a plurality of occurrences of at least one target sequence, wherein the number of labels is m, and number of occurrences of first and second target molecules is n1 and n2 respectively, and the ratio of the greater of n1 and n2 to m is smaller than 0.2.
Claim 39 of the ‘870 patent is drawn to a method that comprises the steps of randomly attaching diverse label sequences from a set of m different label sequences to first target molecule and a second target molecules in a sample, and detecting the new molecule having label attached to the target sequences by detecting the label sequence, wherein the number of label is m, and number of occurrences of first and second target molecule is n1 and n2 respectively, and the ratio of the greater of n1 and n2 to m is smaller than 0.2.
It would have been obvious to an ordinary skilled in the art to utilize the composition of instant claims 1 - 25 in the claimed method of claim 31 of the ‘870 application because the reference application requires the components of Claims 1 - 25 of the present application except the reference application does not recite:
four or more biotin-tagged oligonucleotides containing sequences each complementary to at least one of the four or more distinct target molecules wherein at least one of the four or more distinct target nucleic acid molecules is PIK3R1, MYC, CCND2, or CDKN2A; it would have been obvious to an ordinary skilled in the art that multiple targets may be present in the sample for practice the same method,; it would have been obvious to an ordinary skilled in the art looking at the disclosure of the ‘870 reference application, wherein the method described in [0013] discloses that the method can simultaneously count copies of multiple target sequences, without specifically naming any target sequence. As such, the method claimed in Claims 1 - 25 of the present application is not patentably distinct from the method of claim 31 from the ‘870 reference application.
Therefore, claims 1 - 25 would have been obvious to use in the method as claimed in claim 39 of the ‘870 reference application.
Any additional limitations of the reference application claims are encompassed by the open claim language “comprises” found in the instant claims.
Claims 1-4 and 6-25 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 - 27 of Patent No. 9290808 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because they are both drawn to elements that are used in a method of detecting nucleic acid sequences by attaching diverse sequences (labels) to one end of the sequences to be detected, thus overlapping in scope.
Claims of the present application are drawn to a composition that comprises diverse label sequences and enzymes for attaching these to a plurality of occurrences of at least one target sequence, wherein the number of labels is m, and number of occurrences of first and second target molecules is n1 and n2 respectively, and the ratio of the greater of n1 and n2 to m is smaller than 0.2.
Claim 1 of the ‘808 patent is drawn to a method that comprises the steps of randomly attaching label sequences from a set of m label sequences to first target molecule and a second target molecules in a sample, and detecting the new molecule having label attached to the target sequences by detecting the label sequence, wherein the number of label is m, and number of occurrences of first and second target molecule is n1 and n2 respectively, and the ratio of the greater of n1 and n2 to m is smaller than 0.2.
It would have been obvious to an ordinary skilled in the art to utilize the composition of instant claims 1 - 25 in the claimed method of claim 1 of the ‘808 patent because the reference application requires the components of Claims 1 - 25 of the present application except the patent does not recite:
four or more biotin-tagged oligonucleotides containing sequences each complementary to at least one of the four or more distinct target molecules wherein at least one of the four or more distinct target nucleic acid molecules is PIK3R1, MYC, CCND2, or CDKN2A; it would have been obvious to an ordinary skilled in the art that multiple targets may be present in the sample for practice the same method,; it would have been obvious to an ordinary skilled in the art looking at the disclosure of the ‘808 patent, wherein the method described in [012] discloses that the method can simultaneously count copies of multiple target sequences, without specifically naming any target sequence. As such, the method claimed in Claims 1 - 25 of the present application is not patentably distinct from the method of claim 1 from the ‘808 patent.
Therefore, claims 1 - 25 would have been obvious to use in the method as claimed in claim 1 of the ‘808 patent.
Any additional limitations of the reference application claims are encompassed by the open claim language “comprises” found in the instant claims.
Claims 1-4 and 6-25 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 308 - 335 of Patent No. 9845502 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because they are both drawn to elements that are used in a method of detecting nucleic acid sequences by attaching diverse sequences (labels) to one end of the sequences to be detected, thus overlapping in scope.
Claims of the present application are drawn to a composition that comprises diverse label sequences and enzymes for attaching these to a plurality of occurrences of at least one target sequence, wherein the number of labels is m, and number of occurrences of first and second target molecules is n1 and n2 respectively, and the ratio of the greater of n1 and n2 to m is smaller than 0.2.
Claim 308 of the ‘502 patent is drawn to a method that comprises the steps of randomly attaching label sequences from a set of m label sequences to first target molecule and a second target molecules in a sample, and detecting the new molecule having label attached to the target sequences by detecting the label sequence, wherein the number of label is m, and number of occurrences of first and second target molecule is n1 and n2 respectively, and the ratio of the greater of n1 and n2 to m is smaller than 0.2.
It would have been obvious to an ordinary skilled in the art to utilize the composition of instant claims 1 - 25 in the claimed method of claim 308 of the ‘502 patent because the reference application requires the components of Claims 1 - 25 of the present application except the patent does not recite:
four or more biotin-tagged oligonucleotides containing sequences each complementary to at least one of the four or more distinct target molecules wherein at least one of the four or more distinct target nucleic acid molecules is PIK3R1, MYC, CCND2, or CDKN2A; it would have been obvious to an ordinary skilled in the art that the “plurality of target molecules present in the single cell” recited in reference claim 308 for practice of the method could encompass the recited genes instant claim 1. As such, the method claimed in Claims 1 - 25 of the present application are not patentably distinct from the method of claim 308 from the ‘502 patent.
Therefore, claims 1 - 25 would have been obvious to use in the method as claimed in claim 308 of the ‘502 patent.
Any additional limitations of the reference application claims are encompassed by the open claim language “comprises” found in the instant claims.
Response to Arguments
It is noted the response requests that double patenting rejections be held in abeyance until the rejections outstanding in the instant application are overcome. All the double patenting rejections are maintained for reasons of record (reiterated above).
Conclusion
No claims are 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.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SHABANA MEYERING, Ph.D. whose telephone number is (703)756-4603. The examiner can normally be reached M - F: 9am to 5pm EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Ram Shukla can be reached at (571) 272-0735. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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SHABANA S. MEYERING, Ph.D.
Examiner
Art Unit 1635
/SHABANA S MEYERING/Examiner, Art Unit 1635
/CATHERINE KONOPKA/Primary Examiner, Art Unit 1635
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