DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Interpretation
Attention is directed to MPEP 904.01 [R-08.2012].
The breadth of the claims in the application should always be carefully noted; that is, the examiner should be fully aware of what the claims do not call for, as well as what they do require. During patent examination, the claims are given the broadest reasonable interpretation consistent with the specification. See In re Morris, 127 F.3d 1048, 44 USPQ2d 1023 (Fed. Cir. 1997). See MPEP § 2111 - § 2116.01 for case law pertinent to claim analysis.
It is noted with particularity that narrowing limitations found in the specification cannot be inferred in the claims where the elements not set forth in the claims are linchpin of patentability. In re Philips Industries v. State Stove & Mfg. Co, Inc., 186 USPQ 458 (CA6 1975). While the claims are to be interpreted in light of the specification, it does not follow that limitations from the specification may be read into the claims. On the contrary, claims must be interpreted as broadly as their terms reasonably allow. See Ex parte Oetiker, 23 USPQ2d 1641 (BPAI, 1992). In added support of this position, attention is directed to MPEP 2111 [R-11.2013], where, citing In re Prater, 415 F.2d 1393, 1404-05, 162 USPQ 541, 550-51 (CCPA 1969), is stated:
The court explained that “reading a claim in light of the specification, to thereby interpret limitations explicitly recited in the claim, is a quite different thing from ‘reading limitations of the specification into a claim,’ to thereby narrow the scope of the claim by implicitly adding disclosed limitations which have no express basis in the claim.” The court found that applicant was advocating the latter, i.e., the impermissible importation of subject matter from the specification into the claim.
Additionally, attention is directed to MPEP 2111.01 [R-01.2024], wherein is stated:
II. IT IS IMPROPER TO IMPORT CLAIM LIMITATIONS FROM THE SPECIFICATION
“Though understanding the claim language may be aided by explanations contained in the written description, it is important not to import into a claim limitations that are not part of the claim. For example, a particular embodiment appearing in the written description may not be read into a claim when the claim language is broader than the embodiment.” Superguide Corp. v. DirecTV Enterprises, Inc., 358 F.3d 870, 875, 69 USPQ2d 1865, 1868 (Fed. Cir. 2004).
Attention is also directed to MPEP 2111.02 II [R-07.2022]. As stated herein:
II. PREAMBLE STATEMENTS RECITING PURPOSE OR INTENDED USE
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The claim preamble must be read in the context of the entire claim. The determination of whether preamble recitations are structural limitations or mere statements of purpose or use "can be resolved only on review of the entirety of the [record] to gain an understanding of what the inventors actually invented and intended to encompass by the claim" as drafted without importing "'extraneous' limitations from the specification." Corning Glass Works, 868 F.2d at 1257, 9 USPQ2d at 1966. If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction. Shoes by Firebug LLC v. Stride Rite Children’s Grp., LLC, 962 F.3d 1362, 2020 USPQ2d 10701 (Fed. Cir. 2020) (The court found that the preamble in one patent’s claim is limiting but is not in a related patent); Pitney Bowes, Inc. v. Hewlett-Packard Co., 182 F.3d 1298, 1305, 51 USPQ2d 1161, 1165 (Fed. Cir. 1999). See also Rowe v. Dror, 112 F.3d 473, 478, 42 USPQ2d 1550, 1553 (Fed. Cir. 1997) ("where a patentee defines a structurally complete invention in the claim body and uses the preamble only to state a purpose or intended use for the invention, the preamble is not a claim limitation")… (Emphasis added)
Attention is directed to MPEP 2111 [R-10.2019]. As stated therein:
During patent examination, the pending claims must be "given their broadest reasonable interpretation consistent with the specification." The Federal Circuit’s en banc decision in Phillips v. AWH Corp., 415 F.3d 1303, 1316, 75 USPQ2d 1321, 1329 (Fed. Cir. 2005) expressly recognized that the USPTO employs the "broadest reasonable interpretation" standard:
The Patent and Trademark Office ("PTO") determines the scope of claims in patent applications not solely on the basis of the claim language, but upon giving claims their broadest reasonable construction "in light of the specification as it would be interpreted by one of ordinary skill in the art." In re Am. Acad. of Sci. Tech. Ctr., 367 F.3d 1359, 1364[, 70 USPQ2d 1827, 1830] (Fed. Cir. 2004). Indeed, the rules of the PTO require that application claims must "conform to the invention as set forth in the remainder of the specification and the terms and phrases used in the claims must find clear support or antecedent basis in the description so that the meaning of the terms in the claims may be ascertainable by reference to the description." 37 CFR 1.75(d)(1). (Emphasis added).
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-23 and 25-30 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 148-167 of copending Application No. 19/246,223 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because claims 148-166 are to “a method of spatially barcoding a target nucleic acid in a biological sample” and claim 167 is to “a method of determining a location of a target nucleic acid in a biological sample”.
It is noted that the instant application and the ‘223 application both claim benefit of priority to provisional application 63/436324, filed 12/30/2022.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim Rejections - 35 USC § 112, (b) / Second Paragraph
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Standard for Definiteness.
Attention is directed to MPEP 2171 [R-11.2013]:
Two separate requirements are set forth in 35 U.S.C. 112(b) and pre-AIA 35 U.S.C. 112, second paragraph, namely that:
(A) the claims must set forth the subject matter that the inventor or a joint inventor regards as the invention; and
(B) the claims must particularly point out and distinctly define the metes and bounds of the subject matter to be protected by the patent grant.
The first requirement is a subjective one because it is dependent on what the inventor or a joint inventor for a patent regards as his or her invention. Note that although pre-AIA 35 U.S.C. 112, second paragraph, uses the phrase "which applicant regards as his invention," pre-AIA 37 CFR 1.41(a) provides that a patent is applied for in the name or names of the actual inventor or inventors.
The second requirement is an objective one because it is not dependent on the views of the inventor or any particular individual, but is evaluated in the context of whether the claim is definite — i.e., whether the scope of the claim is clear to a hypothetical person possessing the ordinary level of skill in the pertinent art.
Attention is directed to MPEP 2173.02 I [R-07.2022]:
During prosecution, applicant has an opportunity and a duty to amend ambiguous claims to clearly and precisely define the metes and bounds of the claimed invention. The claim places the public on notice of the scope of the patentee’s right to exclude. See, e.g., Johnson & Johnston Assoc. Inc. v. R.E. Serv. Co., 285 F.3d 1046, 1052, 62 USPQ2d 1225, 1228 (Fed. Cir. 2002) (en banc). As the Federal Circuit stated in Halliburton Energy Servs., Inc. v. M-I LLC, 514 F.3d 1244, 1255, 85 USPQ2d 1654, 1663 (Fed. Cir. 2008):
“We note that the patent drafter is in the best position to resolve the ambiguity in the patent claims, and it is highly desirable that patent examiners demand that applicants do so in appropriate circumstances so that the patent can be amended during prosecution rather than attempting to resolve the ambiguity in litigation.”
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During examination, after applying the broadest reasonable interpretation to the claim, if the metes and bounds of the claimed invention are not clear, the claim is indefinite and should be rejected. Packard, 751 F.3d at 1310 (“[W]hen the USPTO has initially issued a well-grounded rejection that identifies ways in which language in a claim is ambiguous, vague, incoherent, opaque, or otherwise unclear in describing and defining the claimed invention, and thereafter the applicant fails to provide a satisfactory response, the USPTO can properly reject the claim as failing to meet the statutory requirements of § 112(b).”); Zletz, 893 F.2d at 322, 13 USPQ2d at 1322.
Attention is also directed to MPEP 2173.02 III B, which states in part:
To comply with 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph, applicants are required to make the terms that are used to define the invention clear and precise, so that the metes and bounds of the subject matter that will be protected by the patent grant can be ascertained. See MPEP § 2173.05(a), subsection I. It is important that a person of ordinary skill in the art be able to interpret the metes and bounds of the claims so as to understand how to avoid infringement of the patent that ultimately issues from the application being examined. See MPEP § 2173.02, subsection II (citing Morton Int ’l, Inc. v. Cardinal Chem. Co., 5 F.3d 1464, 1470 (Fed. Cir. 1993)); see also Halliburton Energy Servs., 514 F.3d at 1249, 85 USPQ2d at 1658 (“Otherwise, competitors cannot avoid infringement, defeating the public notice function of patent claims.”). Examiners should bear in mind that “[a]n essential purpose of patent examination is to fashion claims that are precise, clear, correct, and unambiguous. Only in this way can uncertainties of claim scope be removed, as much as possible, during the administrative process.” Zletz, 893 F.2d at 322, 13 USPQ2d at 1322 [Fed. Cir. 1989]. (Emphasis added)
Attention is also directed to MPEP 2173.04 [R-10.2019], which states in part:
A broad claim is not indefinite merely because it encompasses a wide scope of subject matter provided the scope is clearly defined. But a claim is indefinite when the boundaries of the protected subject matter are not clearly delineated and the scope is unclear. For example, a genus claim that covers multiple species is broad, but is not indefinite because of its breadth, which is otherwise clear. But a genus claim that could be interpreted in such a way that it is not clear which species are covered would be indefinite (e.g., because there is more than one reasonable interpretation of what species are included in the claim). (Emphasis added)
Holding and Rationale
Claims 1-13, 14-23 and 25-30 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Said claims are deemed to be indefinite with respect to what constitutes the metes and bounds of an “oligonucleotide”. Acknowledgement is made of dependent claim 14 specifying that “the first probe oligonucleotide and the second probe oligonucleotide comprise from 2 to 500 nucleotides in length”. Given that claim 14 must further limit claim 1 from which it depends, it is unclear as to just what is the size, or range(s) in sizes, of the “oligonucleotides” of claim 1 and other dependent claims encompass.
It is noted that claim 30 does not recite any values for thee “oligonucleotides”.
It is further noted that there is no set value for oligonucleotide in the prior art. In support of this position, it is noted that Merriam-Webster.com (“Oligonucleotide definition,” Merriam-Webster.com; accessed 08-23-2017) provides the following exemplary definition:
[A] short nucleic-acid chain usually consisting of up to approximately 20 nucleotides. (Emphasis added)
US 2019/0002971 A1 (Kslover et al.), paragraph [0084], teaches:
In some embodiments, binding moieties comprise an oligonucleotide or analog thereof having a length in the range of from 6 to 60 nucleotides.
US 2009/0011943 A1 (Drmanac et al.), at paragraph [0116], teaches:
The length of capture oligonucleotides may vary widely, In one aspect, capture oligonucleotides and their complements in a bridging oligonucleotide have lengths in the range of from 10 to 100 nucleotides; and more preferably, in the range of from 10 to 40 nucleotides. (Emphasis added)
In comparison, US Patent 6,444,661 B1 (Barton et al.), column 6, first paragraph, states:
The probe oligonucleotide can be as short as about 8-10 bases, up to a length of several thousand bases: the probe can be as long or longer than the target polynucleotide. (Emphasis added)
“Oligonucleotide”, Wikipedia.com (accessed February 17, 2019) teaches:
A less than 100% yield of each synthetic step and the occurrence of side reactions set practical limits of the efficiency of the process so that the maximum length of synthetic oligonucleotides hardly exceeds 200 nucleotide residues. (Emphasis added)
When as here it is evident that there is not a single art-accepted meaning for the term, a question as to the metes and bounds of the claim exist.
Response to traversal
Applicant’s representative, at page 12, bridging to page 13, of the response of 24 January 2025 traverses the rejection of claims as it relates to what constitutes the metes and bounds of an “oligonucleotide”. In support of this position attention is directed to WO2020/176788, which had been incorporated by reference. As asserted to in the response:
Applicant's specification incorporates by reference WO 2020/176788 on page 23, line 2, which states at page 21, lines 16-17 "[t]he terms 'oligonucleotide' and 'polynucleotide' are used interchangeably to refer to a single-stranded multimer of nucleotides from about 2 to about 500 nucleotides in length." (Emphasis added). Therefore, a person of ordinary skill in the art would understand what is claimed with respect to the term "oligonucleotide" in light of the specification. As such, the Office failed to establish a prima facie case of indefiniteness. (Emphasis in original)
The above argument has been considered and has not been found persuasive. It is noted with particularity that narrowing limitations found in the disclosure cannot be read into the claims. In support of this position attention is directed to MPEP 2111.01 [R-01.2024], wherein is stated:
II. IT IS IMPROPER TO IMPORT CLAIM LIMITATIONS FROM THE SPECIFICATION
“Though understanding the claim language may be aided by explanations contained in the written description, it is important not to import into a claim limitations that are not part of the claim. For example, a particular embodiment appearing in the written description may not be read into a claim when the claim language is broader than the embodiment.” Superguide Corp. v. DirecTV Enterprises, Inc., 358 F.3d 870, 875, 69 USPQ2d 1865, 1868 (Fed. Cir. 2004).
It is further noted that a dependent claim must further limit the independent claim that it depends from. As can be seen in dependent claim 14, “the first probe oligonucleotide and the second probe oligonucleotide comprise from 2 to 500 nucleotides in length”. Given the values recited in dependent claim 14, claim 1 from which it depends must be broader; however, there is no indication as to what that value is. It is further noted that the values recited in WO2020/176788 are not any larger. Given such, it is less than clear as to just what does constitute the upper and lower limits in the size range of an oligonucleotide.
In view of the above analysis and in the absence of convincing evidence to the contrary, the rejection is maintained.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1 is/are rejected under 35 U.S.C. 103 as being unpatentable over Frisen et al. (PG Pub No.: US 2015/0344942 A1) in view of Zimmermann et al. (Zimmermann et al. Drug Discovery Today, Vol. 21, No.11 (Nov., 2016), pp: 1828-1834) and Shah et al. (Shah, S. et al. Neuron, Vol. 92 (2016), pp: 342-357).
Frisen et al. (2015), in their abstract, teach steps (a), (c) and (e) of claim 1. As stated therein:
The present invention relates to methods and products for localized or spatial detection and/or analysis of RNA in a tissue sample or a portion thereof, comprising: (a) providing an object substrate on which at least one species of capture probe, comprising a capture domain, is directly or indirectly immobilized such that the probes are oriented to have a free 3′ end to enable said probe to function as a reverse transcriptase (RT) primer; (b) contacting said substrate with a tissue sample and allowing RNA of the tissue sample to hybridise to the capture probes; (c) generating cDNA molecules from the captured RNA molecules using said capture probes as RT primers; (d) labelling the cDNA molecules generated in step (c), wherein said labelling step may be contemporaneous with, or subsequent to, said generating step; (e) detecting a signal from the labelled cDNA molecules; and optionally (f) imaging the tissue sample, wherein the tissue sample is imaged before or after step (c).
Frisen et al. (2015), at paragraph [0122], teach:
[0122] In a preferred embodiment the positional domain of each species of capture probe contains a unique barcode sequence. The barcode sequences may be generated using random sequence generation. The randomly generated sequences may be followed by stringent filtering by mapping to the genomes of all common reference species and with pre-set Tm intervals, GC content and a defined distance of difference to the other barcode sequences to ensure that the barcode sequences will not interfere with the capture of the nucleic acid, e.g. RNA from the tissue sample and will be distinguishable from each other without difficulty. (Emphasis added)
Frisen et al. (2015), at claim 13, teach:
13. The method of claim 1, wherein the capture probes further comprise a positional domain which is 5′ relative to the capture domain, wherein said positional domain comprises a sequence that corresponds to the position of the capture probe on the object substrate, preferably wherein the positional domain of each species of capture probe comprises a unique barcode sequence. (Emphasis added)
Frisen et al. (2015), at paragraph [0023], teach:
[0023] For instance, quantifying the relative abundance of the labelled cDNA may be used to determine the transcriptional activity of different regions of a tissue sample, e.g. to identify cells with high or no transcriptional activity. The method can be used to determine the optimum reaction conditions for detecting, e.g. capturing, the transcriptome of a tissue sample on an object substrate, e.g. by repeating the method using different conditions (e.g. conditions for permeabilizing the tissue to allow the nucleic acids in the tissue sample to interact with the immobilized primers on the substrate), comparing the intensity and/or resolution of the signal obtained from labelled cDNA molecules on the imaged substrates and optionally selecting the conditions that provide the optimum image intensity and/or resolution.
Zimmermann et al. (2016) teach the ligation step (See Figure 3) recited in step (d) and (f) of claim 1 of 18/745,320 (See for example Figure 3 of Zimmermann et al.)
Shah et al. (2016) teaches step (b) of claim 1 of 18/745,320 (See left column page 355 of Shah et al.). As stated therein:
Sample Permeabilization, Hybridization, and Imaging
Sections were permeabilized in 4 °C 70% EtOH for 12–18 hr. Brains were further
permeabilized by the addition of RNase-free 8% SDS. (Emphasis added)
In view of the above presentation, it would have been quite obvious to one of ordinary skill in the art to have adapted the methods of Frisen et al. (2015), Zimmermann et al. (2016), and Shah et al. (2016) so to develop a method of using combinations of barcoded probes so to detect the location of target sequences in mRNA.
In view of the well developed state of the art, said ordinary artisan would have been quite motivated and would have had a most reasonable expectation of success.
In view of thee above analysis and in the absence of convincing evidence to the contrary, claim 1 is rejected under 35 U.S.C. 103 as being unpatentable over Frisen et al. (PG Pub No.: US 2015/0344942 A1) in view of Zimmermann et al. (Zimmermann et al. Drug Discovery Today, Vol. 21, No.11 (Nov., 2016), pp: 1828-1834) and Shah et al. (Shah, S. et al. Neuron, Vol. 92 (2016), pp: 342-357).
Claim(s) 2 is/are rejected under 35 U.S.C. 103 as being unpatentable over Frisen et al. (PG Pub No.: US 2015/0344942 A1) in view of Zimmermann et al. (Zimmermann et al. Drug Discovery Today, Vol. 21, No.11 (Nov., 2016), pp: 1828-1834) and Shah et al. (Shah, S. et al. Neuron, Vol. 92 (2016), pp: 342-357) as applied to claim 1 above, and further in view of US 2022/0106632 A1 (Galonska et al.).
See above for the basis of the rejection as it pertains to the teachings of Frisen et al., Zimmermann et al., and Shah et al.
Neither Frisen et al., Zimmermann et al., nor Shah et al., have been found to teach explicitly of having probes hybridize so adjacent sequences.
Galonska et al., at paragraph [0097], teach of a method of hybridizing first and second oligonucleotide probes to adjacent sequences. As disclosed therein:
[Of] a process that includes multiple oligonucleotides (also called “oligonucleotide probes” or simply “probes,” and a pair of probes can be called interchangeably “first probes” and “second probes,” or “first probe oligonucleotides” and “second probe oligonucleotides,”) that hybridize to adjacent complementary analyte (e.g., mRNA) sequences. (Emphasis added)
In view of the above showing, it would have been quite obvious to one of ordinary skill in the art at the time of the invention to have modified the method of Frisen et al., Zimmermann et al., and Shah et al. with that of Galonska et al., wherein one was selecting adjacent target sequences in mRNA and selecting oligonucleotide probes that would hybridize to such adjacent sequences.
In view of such explicit teachings and the well developed state of the art, said ordinary artisan would have been amply motivated and would have had a most reasonable expectation of success.
Claim(s) 3 is/are rejected under 35 U.S.C. 103 as being unpatentable over Frisen et al. (PG Pub No.: US 2015/0344942 A1) in view of Zimmermann et al. (Zimmermann et al. Drug Discovery Today, Vol. 21, No.11 (Nov., 2016), pp: 1828-1834) and Shah et al. (Shah, S. et al. Neuron, Vol. 92 (2016), pp: 342-357) as applied to claim 1 above, and further in view of US 2020/0362392 A1 (Nolan).
See above for the basis of the rejection as it pertains to the teachings of Frisen et al., Zimmermann et al., and Shah et al.
Neither Frisen et al., Zimmermann et al., nor Shah et al., have been found to teach explicitly of having probes hybridize so non-adjacent sequences.
Nolan, at paragraph [0017], teaches:
[0017] Also disclosed herein is a method for detection of a target mRNA sequence, the method comprising: (a) lysing a cell sample to release mRNA; (b) contacting the lysed cell sample with a plurality of beads, wherein a bead comprises a plurality of tethered oligonucleotide sequences capable of hybridizing to the released mRNA molecules; (c) annealing a first oligonucleotide proximity probe with the hybridized mRNA molecules on the plurality of beads, wherein the first oligonucleotide proximity probe comprises an epitope specific barcode sequence and a first target recognition sequence that is capable of hybridizing to a first segment of the target nucleic acid sequence; (d) annealing a second oligonucleotide proximity probe with the hybridized mRNA molecules on the plurality of beads, wherein the second oligonucleotide proximity probe comprises a second target recognition sequence that is capable of hybridizing to a second segment of the target nucleic acid sequence, and wherein the first and second segments of the target nucleic acid sequence are different and are separated from each other by a specified number of nucleotides, N; (e) annealing a bridge oligonucleotide with the hybridized oligonucleotide proximity probes on the plurality of beads, wherein the bridge oligonucleotide comprises two probe recognition sequences, wherein the first probe recognition sequence is capable of hybridizing to a segment of the first oligonucleotide proximity probe, and the second probe recognition sequence is capable of hybridizing to a segment of the second oligonucleotide proximity probe, thereby creating a target specific probe complex that includes the epitope specific barcode; and (f) ligating the annealed oligonucleotide proximity probes and bridge oligonucleotide to create a covalently joined target specific probe complex. (Emphasis added)
As evidenced above, Nolan teaches explicitly of having a first and second oligonucleotide probe hybridize to target sequences of a common mRNA molecule, but are separated from one another a known number of nucleotides.
In view of such explicit teachings, it would have been quite obvious to an ordinary artisan to have selected first and second probes that would hybridize to different targets in a common mRNA molecule, yet are separated from one another by a known distance.
In view of the detailed teachings and broad applicability of such methods, the ordinary artisan would have been amply motivated and would have had a most reasonable expectation of success. Given such, and in the absence of convincing evidence to the contrary, claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Frisen et al. (PG Pub No.: US 2015/0344942 A1) in view of Zimmermann et al. (Zimmermann et al. Drug Discovery Today, Vol. 21, No.11 (Nov., 2016), pp: 1828-1834) and Shah et al. (Shah, S. et al. Neuron, Vol. 92 (2016), pp: 342-357) as applied to claim 1 above, and further in view of US 2020/0362392 A1 (Nolan).
Conclusion
Objections and/or rejections which appeared in the prior Office action and which have not been repeated hereinabove have been withdrawn.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Bradley L. Sisson whose telephone number is (571)272-0751. The examiner can normally be reached Monday to Thursday, from 6:30 AM to 5 PM.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Wu-Cheng Shen can be reached at 571-272-3157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Bradley L. Sisson/Primary Examiner, Art Unit 1682