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 a method of circularizing a circularizable probe comprising splint oligonucleotides (claims 77-78 and 81-83) and a single nucleotide (claim 80) in the reply filed on June 22nd, 2026 is acknowledged.
Claims 79, 84, and 85 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on June 22nd, 2026.
Information Disclosure Statement
The information disclosure statements (IDSs) submitted on April 29th, 2024 and June 22nd, 2026 are acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements have been considered by the examiner.
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Claim Summary
Claims 76-77, 82-83, 87, 89-91, and 93-94 have been amended. Claims 1-75 have been canceled. Claims 76-95 are pending. Claims 79, 84, and 85 are withdrawn from consideration as being drawn to a non-elected invention/species. Claims 76-78, 80-83, and 86-95 are under examination and discussed in this Office action.
Specification
The use of terms such as VENT, Phusion, and Cy5, which are trade names or marks used in commerce, has been noted in this application. All terms should be accompanied by the generic terminology; furthermore the terms 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 § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 76-78, 80-83, 86-88, 92, and 94-95 are rejected under 35 U.S.C. 103 as being unpatentable over Lizardi (US 6143495 A), in view of Church (US 20140349294 A1) and Mignardi (Oligonucleotide gap-fill ligation for mutation detection and sequencing in situ, Nucleic Acids Research, December 2015, 43, 1-12).
Regarding instant claim 76, Lizardi teaches a method for analyzing a biological sample, comprising: (a) contacting the biological sample with a circularizable probe (Column 2, lines 64-67 to Column 3, lines 1-4), wherein the circularizable probe comprises a first probe region and a second probe region that hybridize to a first target sequence and a second target sequence, respectively, in a target nucleic acid in the biological sample (Column 8, lines 37-50; Column 9, lines 26-39), wherein the first target sequence and the second target sequence are separated by a gap sequence in the target nucleic acid (Column 9, lines 45-47), and wherein the gap sequence comprises a variant sequence from among a plurality of different sequences (Column 12, lines 37-44); (b) circularizing the circularizable probe to generate a circularized probe comprising a gap-filled region complementary to the gap sequence (Column 9, lines 5-7); (c) generating a rolling circle amplification product (RCP) of the circularized probe in the biological sample, wherein the RCP comprises multiple copies of the gap sequence (Column 9, lines 5-9). Lizardi further teaches on the use of detection probes that may hybridize to detection tags on the circularizable probe (Column 15, lines 13-32).
Lizardi does not teach (d) contacting the biological sample with a plurality of nucleic acid probes, wherein each nucleic acid probe of the plurality of nucleic acid probes: (i) comprises a hybridization region complementary to one of the plurality of different sequences; and (ii) is detectably labeled or comprises a detectable region that directly or indirectly binds to a detection oligonucleotide comprising a detectable label, wherein a nucleic acid probe of the plurality of nucleic acid probes hybridizes to the RCP at a copy of the gap sequence comprising the variant sequence; and (e) detecting a signal associated with the nucleic acid probe hybridized to the RCP at a location in the biological sample, thereby identifying the variant sequence at the location in the biological sample.
Church, in a reasonably pertinent field, teaches contacting a biological sample with a plurality of nucleic acid probes (Page 1, paragraph [0004]), wherein each nucleic acid probe of the plurality of nucleic acid probes: (i) comprises a hybridization region complementary to one of a plurality of different sequences (Page 1, paragraph [0004]; Page 2, paragraphs [0008]-[0009]); and (ii) comprises a detectable region that directly binds to a detection oligonucleotide comprising a detectable label (Page 1, paragraph [0004]; Page 2, paragraphs [0008]-[0009]). Church teaches a set of probes corresponding to A, C, G, or T in a particular position (Page 2, paragraph [0008]-[0009]), which reasonably represents a variant sequence, and detectable moieties that specifically identify each of A, C, G, or T in the position (Page 2, paragraph [0008]-[0009]). Church also teaches on hybridization of probes to a nucleic acid sequence (Page 1, paragraph [0004]). As taught by Lizardi, replication of the circularizable probe produces a nucleic acid sequence (Column 9, lines 5-9), which could reasonably be hybridized by the probes of Church.
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the method of Lizardi with the probes of Church. Since Church teaches on detection probes capable of detecting variant sequences, which is reasonably pertinent to the gap oligonucleotides of Lizardi, one of ordinary skill in the art would combine the two teachings with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to make this modification because Church’s probes may be applied with particular advantage to determine the identify of oligonucleotide sequences (Church, Page 4, paragraph [0035]).
Neither of these references teach (e) detecting a signal associated with the nucleic acid probe hybridized to the RCP at a location in the biological sample, thereby identifying the variant sequence at the location in the biological sample.
Mignardi, in the same field of endeavor as Lizardi, teaches detecting a signal associated with a nucleic acid probe hybridized to an RCP at a location in the biological sample (Page 6, column 1, paragraph 1), thereby identifying a variant sequence at the location in the biological sample (Figure 3E). Mignardi teaches on using padlock probes and gap fill ligation with gap oligonucleotides to perform this detection of wild-type or mutant forms of target nucleic acids (Page 4, column 2, paragraph 4 to Page 5, column 1, paragraph 1; Figure 1)
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the method of Lizardi, in view of Church, with detecting the signal in a location in the sample of Mignardi. Since both Lizardi and Mignardi are in the same field of endeavor (e.g. circularized probes for analyzing biological samples), one of ordinary skill in the art would combine the two teachings with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to make this modification because padlock gap probes and oligonucleotide gap-fill ligation can be used for highly specific in situ mutational analysis (Mignardi, Page 2, column 1, paragraph 3).
Regarding instant claim 77, Lizardi, in view of Church and Mignardi, teaches the method of claim 76. Lizardi further teaches wherein the circularizing in (b) comprises contacting the biological sample with a library of splint oligonucleotides (Column 12, lines 37-44), wherein each splint oligonucleotide comprises: (i) ligatable ends (column 12, lines 25-27); and iii) a hybridization region complementary to one of the plurality of different sequences, wherein a splint oligonucleotide of the library of splint oligonucleotides that is complementary to the gap sequence is ligated to the circularizable probe, thereby circularizing the circularizable probe to generate the circularized probe (Column 12, lines 20-31 and 37-44).
Regarding instant claim 78, Lizardi, in view of Church and Mignardi, teaches the method of claim 77. Lizardi further teaches wherein the gap sequence is between 2 and 40 nucleotides in length (Column 9, lines 53-54).
Regarding instant claim 80, Lizardi, in view of Church and Mignardi, teaches the method of claim 76. Mignardi further teaches wherein the variant sequence is a single nucleotide in length (Figure 1 and caption).
Regarding instant claim 81, Lizardi, in view of Church and Mignardi, teaches the method of claim 77. Lizardi further teaches wherein the splint oligonucleotide is ligated to the circularizable probe by a ligase using the target nucleic acid as a template (Column 12, lines 25-28).
Regarding instant claim 82, Lizardi, in view of Church and Mignardi, teaches the method of claim 77. Lizardi further teaches wherein the library of splint oligonucleotides comprises multiple oligonucleotides (e.g. at least 2) of different sequences (Column 12, lines 37-39).
Regarding instant claim 83, Lizardi, in view of Church and Mignardi, teaches the method of claim 77. Mignardi further teaches wherein the molar concentration of the library of splint oligonucleotides is about 10, or more times the molar concentration of the circularizable probe (Page 3, column 1).
Regarding instant claim 86, Lizardi, in view of Church and Mignardi, teaches the method of claim 76. Church further teaches wherein the hybridization region in each nucleic acid probe is 6 nucleotides in length (Figure 1: L1).
Regarding instant claim 87, Lizardi, in view of Church and Mignardi, teaches the method of claim 76. Church further teaches wherein the plurality of nucleic acid probes comprises between 2 and 20 different nucleic acid probes comprising different hybridization regions, wherein each hybridization region is complementary to a different one of the plurality of different sequences (Page 2, paragraphs [0008]-[0009]: at least 4 options given the four different available single nucleotides A, C, G, or T).
It is noted that the courts have found that “where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists.” In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). Thus, the 4 options of Church would be obvious because they fall within the claimed range of between 2 and 20 different nucleic acid probes.
Regarding instant claim 88, Lizardi, in view of Church and Mignardi, teaches the method of claim 76. Church further teaches wherein the detectable region is in a 5' overhang or a 3' overhang of the nucleic acid probe that hybridizes to the copy of the gap sequence in the RCP (Figure 1: B1).
Regarding instant claim 92, Lizardi, in view of Church and Mignardi, teaches the method of claim 76. Lizardi further teaches wherein the target nucleic acid is a target RNA (Column 31, lines 35-39).
Regarding instant claim 94, Lizardi, in view of Church and Mignardi, teaches the method of claim 76. Mignardi further teaches wherein the first probe region and the second probe region are common among a plurality of circularizable probes each targeting a target nucleic acid molecule comprising a different variant sequence of the gap sequence (Table 1: Padlock Gap Probes), and the different variant sequences are at different positions in the gap sequence (Table 1: Gap Probes).
Regarding instant claim 95, Lizardi, in view of Church and Mignardi, teaches the method of claim 76. Mignardi further teaches wherein the biological sample is a cell (Page 5, column 2, paragraph 2 to Page 6, column 1, paragraph 1; Figure 3) or tissue sample comprising cells or cellular components (Page 6, column 2, paragraph 2 to Page 7, column 1; Figure 6).
Claims 89-91 are rejected under 35 U.S.C. 103 as being unpatentable over Lizardi (US 6143495 A), Church (US 20140349294 A1) and Mignardi (Oligonucleotide gap-fill ligation for mutation detection and sequencing in situ, Nucleic Acids Research, December 2015, 43, 1-12), as applied to claims 76-78, 80-83, 86-88, 92, and 94-95 above, and further in view of Sood (US 20080118916 A).
Regarding instant claim 89, Lizardi, in view of Church and Mignardi, teaches the method of claim 76. Church teaches contacting a biological sample with a plurality of nucleic acid probes (Page 1, paragraph [0004]), wherein each nucleic acid probe of the plurality of nucleic acid probes: (i) comprises a hybridization region complementary to one of a plurality of different sequences (Page 1, paragraph [0004]; Page 2, paragraphs [0008]-[0009]); and (ii) comprises a detectable region that directly binds to a detection oligonucleotide comprising a detectable label (Page 1, paragraph [0004]; Page 2, paragraphs [0008]-[0009]). Church teaches a set of probes corresponding to A, C, G, or T in a particular position (Page 2, paragraph [0008]-[0009]), which reasonably represents a variant sequence, and detectable moieties that specifically identify each of A, C, G, or T in the position (Page 2, paragraph [0008]-[0009]). Church also teaches on hybridization of probes to a nucleic acid sequence (Page 1, paragraph [0004]).
None of these references teach wherein one or more of the plurality of different sequences are assigned a signal code sequence, and detecting the one or more of the plurality of different sequences comprises: (I) contacting the biological sample with a first nucleic acid probe and a first detection oligonucleotide to generate a first complex; (II) imaging the biological sample to detect a first signal from the first detectable label, wherein the first signal corresponds to a first signal code in the signal code sequence; (III) contacting the biological sample with a second nucleic acid probe and a second detection oligonucleotide to generate a second complex; and (IV) imaging the biological sample to detect a second signal from the second detectable label, wherein the second signal corresponds to a second signal code in the signal code sequence, wherein the signal code sequence comprising at least the first signal code and the second signal code is determined based on signals detected at the location in the biological sample, thereby identifying the one or more of the plurality of different sequences at the location in the biological sample.
Sood, in a reasonably pertinent field, teaches iterative detection of multiple targets in a biological sample (Page 1, paragraph [0004]). Sood teaches contacting the sample with a first probe, binding the first probe to the first target, observing the first signal from the first probe, and applying a chemical agent to modify the first signal (Page 1, paragraph [0004]). Sood further teaches contacting the sample with a second probe, physically binding the second probe to a second target, and observing a second signal from the second probe (Page 1, paragraph [0004]). Sood teaches the probes may comprise binders and signal generators (e.g. nucleic acid probes and detection oligonucleotides; Pages 5-6, paragraph [0068]), the binders comprising a nucleic acid (Page 7, paragraph [0082]) and the signal generators being nucleic acid in nature (Page 9, paragraph [0094]) with one of many different options of detectable signal (Pages 9-10, paragraph [0098]-[0101]). Finally, Sood teaches wherein the signal code sequence comprising at least the first signal code and the second signal code is determined based on signals detected at the location in the biological sample, thereby identifying the one or more of the plurality of different sequences at the location in the biological sample (Page 14, paragraphs [0133] and [0135]).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the method of Lizardi, in view of Church and Mignardi, with the iterative detection of multiple targets of Sood. Since Sood teaches on detection of targets in a biological sample, which is reasonably pertinent to Lizardi, in view of Church and Mignardi, one of ordinary skill in the art would combine the two teachings with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to make this modification because it allows for detecting a plurality of targets in the same biological sample with little or no effect on the integrity of the biological sample (Sood, Pages 3-4, paragraph [0050]).
Regarding instant claim 90, Lizardi, in view of Church, Mignardi, and Sood, teaches the method of claim 89. Church teaches contacting a biological sample with a plurality of nucleic acid probes (Page 1, paragraph [0004]), wherein each nucleic acid probe of the plurality of nucleic acid probes: (i) comprises a hybridization region complementary to one of a plurality of different sequences (Page 1, paragraph [0004]; Page 2, paragraphs [0008]-[0009]); and (ii) comprises a detectable region that directly binds to a detection oligonucleotide comprising a detectable label (Page 1, paragraph [0004]; Page 2, paragraphs [0008]-[0009]). Church teaches a set of probes corresponding to A, C, G, or T in a particular position (Page 2, paragraph [0008]-[0009]), which reasonably represents a variant sequence, and detectable moieties that specifically identify each of A, C, G, or T in the position (Page 2, paragraph [0008]-[0009]). Church also teaches on hybridization of probes to a nucleic acid sequence (Page 1, paragraph [0004]).
Sood further teaches wherein the contacting in (I) comprises contacting the biological sample with a first pool of nucleic acid probes and the contacting in (III) comprises contacting the biological sample with a second pool of nucleic acid probes (Page 11, paragraph [0112]). Sood does not explicitly teach contacting with a universal pool of detection oligonucleotides. However, Sood teaches that four different probes may be employed at once with fluorescent-based signal generators (Page 11, paragraph [0113]). Sood also teaches that multiple probes may be used at once (Page 11, paragraph [0112]). If multiple probes are applied at once, multiple signal generators could be applied at once (e.g. universal pool of detection oligonucleotides). Therefore, it would be obvious that there is the option to use a universal pool of detection oligonucleotides instead of one at a time, which would amount to simple substitution of one known element for another to obtain predictable results (see MPEP 2141(III)).
Regarding instant claim 91, Lizardi, in view of Church, Mignardi, and Sood, teaches the method of claim 90. Church further teaches on different detectable moieties associated with each of A, C, T, or G at a particular position in the target sequence (Page 2, paragraph [0008]). Church also teaches that this approach of using different moieties for different nucleotides can be applied to any nucleotide within the target sequence (Page 2, paragraph [0008]). Therefore, it would be obvious that multiple different subsets of the plurality of different sequences in the biological sample could be identified, wherein each subset is assigned a different signal code sequence, given that Church indicates the use of different detectable moieties dependent on the nucleotide being detected.
Claim 93 is rejected under 35 U.S.C. 103 as being unpatentable over Lizardi (US 6143495 A), Church (US 20140349294 A1) and Mignardi (Oligonucleotide gap-fill ligation for mutation detection and sequencing in situ, Nucleic Acids Research, December 2015, 43, 1-12), as applied to claims 76-78, 80-83, 86-88, 92, and 94-95 above, and further in view of Bernitz (US 20140120534 A1).
Regarding instant claim 93, Lizardi, in view of Church and Mignardi, teaches the method of claim 76.
None of these references teach wherein the circularized probe comprises a barcode sequence corresponding to the target nucleic acid or a sequence thereof, wherein the barcode sequence is not complementary to the target nucleic acid or the sequence thereof.
Bernitz, in the same field of endeavor, teaches wherein a circularized probe comprises a barcode sequence corresponding to the target nucleic acid or a sequence thereof (Page 6, paragraph [0046]), wherein the barcode sequence is not complementary to the target nucleic acid or the sequence thereof (Page 6, paragraph [0046]).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the circularized probe of Lizardi, in view of Church and Mignardi, with the barcode sequence of Bernitz. Since both Lizardi and Bernitz are in the same field of endeavor (e.g. analyzing biological samples with circularized probes), one of ordinary skill in the art would combine the two teachings with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to make this modification because a barcode sequence can be used to identify the nucleic acid that an RCA product relates to (Bernitz, Page 6, paragraph [0046]).
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 76-78, 80-83, and 86-95 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 136-155 of copending Application No. 18960940 in view of Lizardi (US 6143495 A), Church (US 20140349294 A1), Mignardi (Oligonucleotide gap-fill ligation for mutation detection and sequencing in situ, Nucleic Acids Research, December 2015, 43, 1-12), and Sood (US 20080118916 A).
Although the claims at issue are not identical, they are not patentably distinct from each other because both the ‘940 reference application and the instant application claim a method for analyzing a biological sample, comprising: (a) contacting the biological sample with a circularizable probe, wherein the circularizable probe comprises a first probe region and a second probe region that hybridize to a first target sequence and a second target sequence, respectively, in a target nucleic acid in the biological sample, wherein the first target sequence and the second target sequence are separated by a gap sequence in the target nucleic acid, and wherein the gap sequence comprises a variant sequence; (b) circularizing the circularizable probe to generate a circularized probe comprising a gap-filled region complementary to the gap sequence; (c) generating a rolling circle amplification product (RCP) of the circularized probe in the biological sample, wherein the RCP comprises multiple copies of the gap sequence; (d) contacting the biological sample with a probe complementary to the variant sequence (e) detecting a signal associated with the probe hybridized to the gap sequence in the RCP at a location in the biological sample, thereby identifying the variant sequence at the location in the biological sample (instant claim 76; reference claim 136).
The ‘940 reference application and the instant application both further claim wherein the circularizing comprises contacting the biological sample with a library of splint oligonucleotides, wherein each splint oligonucleotide comprises: (i) ligatable ends; and (ii) a hybridization region complementary to one of the plurality of different sequences, wherein a splint oligonucleotide of the library of splint oligonucleotides that is complementary to the gap sequence is ligated to the circularizable probe, thereby circularizing the circularizable probe to generate the circularized probe (instant claim 77; reference claim 137); wherein the splint oligonucleotide is ligated to the circularizable probe by a ligase using the target nucleic acid as a template (instant claim 81; reference claim 139); wherein the circularized probe comprises a barcode sequence corresponding to the target nucleic acid or a sequence thereof, wherein the barcode sequence is not complementary to the target nucleic acid or the sequence thereof (instant claim 93; reference claim 146); wherein one or more of the plurality of different sequences are assigned a signal code sequence, and detecting the one or more of the plurality of different sequences comprises: contacting the biological sample with detection probes in rounds, imaging in between rounds to generate a signal code sequence, thereby identifying the one or more of the plurality of different sequences of the target nucleic acid at the location in the biological sample (instant claim 89; reference claim 150); and wherein the biological sample is a cell or tissue sample comprising cells or cellular components (instant claim 95; reference claim 155).
The ‘940 claims do not require aspects related to the splint oligonucleotide or gap sequence being between 2 and 40 nucleotides in length; the variant sequence being a single nucleotide in length; the library of splint oligonucleotides comprise at least 2 or at least 10 oligonucleotides of different sequences; particular molar concentration ratios between the circularizable probe and the splint oligonucleotides; the hybridization region in each probe being between 6 and 18 nucleotides in length; the plurality of nucleic acid probes comprising between 2 and 20 different nucleic acid probes comprising different hybridization regions; the detection region of the nucleic acid probe being a 5’ overhang or a 3’ overhang; methods relating to pools of nucleic acid probes and universal pools of detection oligonucleotides; identifying multiple different subsets of different sequences, where each subset is assigned a different signal code sequence; or wherein the first probe region and the second probe region are common among a plurality of circularizable probes each targeting a target nucleic acid molecule comprising a different variant sequence of the gap sequence, and the different variant sequences are at different positions in the gap sequence. However, Lizardi, Church, Mignardi, and Sood teach the claimed limitations as discussed in the above 103 rejections, obviating these variations to the claims of the ‘940 application. Any additional limitations of the claims of copending Application No. 18960940 are encompassed by the open claim language "comprising" found in the instant claims.
This is a provisional nonstatutory double patenting rejection.
Conclusion
All claims stand rejected.
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/ALLISON E SCHLOOP/Examiner, Art Unit 1683
/Robert T. Crow/Primary Examiner, Art Unit 1683
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