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 .
Detailed Action
This office action is a response to applicant’s communication submitted December 22, 2025, wherein claims 8, 12, and 15 are amended and new claims 26 and 27 are introduced. This application is a national stage application of PCT/GB2021/051109, filed May 7, 2021, which claims benefit of foreign application GB2006803.7, filed May 7, 2020.
Claims 1-16, 18-23, and 25-28 are pending in this application.
Claims 21-23 are withdrawn from consideration.
Claims 1-16, 18-20, and 25-28 as amended are examined on the merits herein.
Withdrawn Rejections
Applicant’s amendment, submitted December 22, 2025, with respect to the rejection of claims 8, 12, and 15 under 35 USC 112(b) for indefinitely reciting broad limitations followed by narrower preferred limitations, has been fully considered and found to be persuasive to remove the rejection as the claims have been amended so as to remove the preferred limitations. Therefore the rejection is withdrawn.
Applicant’s arguments, submitted December 22, 2025, with respect to the rejection of claims 1-3, 5-11, 14, 16, 19, and 20 under 35 USC 103 for being obvious over Van Nostrand et al. in view of Enroth et al., have been fully considered and found to be persuasive to remove the rejection as Applicant persuasively argues that the method described by Enroth involves a different exonuclease that functions in a different manner. Therefore the rejection is withdrawn.
The following rejections of record in the previous action are maintained:
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.
Claims 1, 2, 3, 5-11, 14-16, 19, 20, and 26 are rejected under 35 U.S.C. 103 as being unpatentable over Van Nostrand et al. (Chapter 14 of mRNA processing, published by Humana Press, Reference of record in previous action) in view of Cao Bo. (Chinese patent publication CN109161586A, Reference and English machine translation of record in previous action)
Independent claim 1 claims a process comprising steps of cross-linking a RNA molecule and a RNA-binding protein in a sample, contacting the sample with an agent that cleaves the crosslinked RNA to shorten said RNA, purifying the cross-linked complex, contacting the complex with an adaptor containing a detection means, removing unbound adaptor, isolating the adaptor-bound crosslinked complex, and visualizing said complex. Dependent claim 2 requires additional steps comprising partially digesting the RBP, purifying the RNA, and preparing it for high-throughput sequencing. Dependent claim 3 specifies the agent used to purify the RNB-RNA complex as being, for example, an antibody. Independent claim 5 describes a similar process further comprising steps of partially digesting the RNA binding protein, purifying the RNA, and preparing the RNA for high-throughput sequencing. Note that the term “detecting means” describing a portion of the adaptor, is generic to any molecular structure that could be detected by any method, including simply unmodified DNA or RNA that could be detected by hybridization or fluorescence, for example.
Van Nostrand et al. discloses an enhanced CLIP (eCLIP) protocol for isolation of RNA targets of RNA binding proteins. (p. 178 second and third paragraph) The process involves steps of UV-crosslinking cells comprising a RNA-binding protein, lysis of the crosslinked cells, RNAse-mediated fragmentation of the cells, immunoprecipitation or the RBP, ligation to a 3’- adaptor, isolation on a polyacrylamide gel, proteinase K treatment to remove the RBP, purifying the RNA library, and then reverse transcribing the RNA library to create a cDNA library, which is suitable for high-throughput sequencing. (See p. 183 figure 1) This process is reasonably considered to include all of the limitations of claims 1, 2, and 5, with the exception of the use of an exonuclease digestion to remove unligated adaptor.
However, Cao Bo discloses a method of reverse transcribing RNA to form a cDNA library for high-throughput sequencing, including steps of ligating RNA to DNA linkers and then removing excess linker. (abstract, also p. 4 paragraph 7) Preferably the exonuclease is RecJ. (p. 4 paragraph 10) It would therefore have been obvious to one of ordinary skill in the art at the time of the invention to incorporate an additional exonuclease treatment step into the protocol described by Van Nostrand et al. One of ordinary skill in the art would have found this to be obvious in view of the fact that such a removal step is described by Cao Bo to be useful in a similar process of cDNA library synthesis.
With respect to the limitation in claims 5 and 6 requiring that step C uses an agent that “specifically interacts with protein side chains,” and comprises a carboxyl group, these limitations are fairly broad and do not specify any particular structure or class of compound used. Therefore without further limitation they are seen to encompass antibodies which are specific for certain binding partners, interact with protein side chains, and contain carboxyl groups. Therefore these limitations are met by the process described by Van Nostrand.
With respect to claim 7, as discussed above, Van Nostrand describes a cell lysis step. (p. 182 section 3.2.1)
Regarding claim 8, Von Nostrand describes both UV crosslinking and RNA fragmentation with RNAse I. (p. 182 section 3.1.2, p. 184 section 3.2.2)
Regarding claim 9, Von Nostrand describes the antibody as coupled to magnetic beads. (p. 184 section 3.3)
Regarding claim 10, Van Nostrand describes a washing step immediately after capturing the complexes on the beads. (p. 184 section 3.4)
Regarding claims 11 and 14, Van Nostrand discloses using the adapter InvRiL19. (p. 186 section 3.5.2) The sequence of this adaptor is seen to have 23 nucleotides and to be 5’- adenylated. (p. 181 section 2.4)
Regarding claim 16, Von Nostrand discloses a reverse transcription protocol comprising steps of reverse transcribing cDNA from the RNA,, digesting the primers with ExoSAP-IT, immobilization of the cDNA on silane beads, ligating a linker (primer) onto the bead, and performing PCR on the cDNA. (pp. 191-193, sections 3.9-3.11)
Regarding claim 19, Van Nostrand describes purification of the PCR products. (p. 194 section 3.11.3)
Regarding claim 20, Van Nostrand discloses that CLIP techniques are used to prepare libraries for high-throughput sequencing. (p. 178 second paragraph) This would suggest to one of ordinary skill in the art to carry out high throughput sequencing on a cDNA library prepared by this method, rendering claim 20 obvious.
For these reasons the invention taken as a whole is prima facie obvious.
Claim 13 is rejected under 35 U.S.C. 103 as being unpatentable over Van Nostrand in view of Cao Bo as applied to claims 1, 2, 3, 5-11, 14-16, 19, 20, and 26 above, and further in view of Correa et al. (PCT international publication WO2020/231697, Reference of record in previous action)
The disclosures of Van Nostrand and Cao Bo are discussed above. Van Nostrand in view of Cao Bo does not specifically disclose ligating an adaptor having one of the sequences recited in claim 13. However, Correa et al. discloses a method of preparing a population of nucleotides. (p. 1 paragraphs 28-32) Correa further describes using reverse transcription from a polynucleotide to which a 3’- adaptor has been attached. (p. 3 lines 10-15, also figures 4A-C) Adaptor sequences include Seq ID No:11-16 or 18, (See p. 29 table 1) which comprise present Seq ID No: 1 as recited in claim 13, for example. It would therefore have been obvious to one of ordinary skill in the art at the time of the invention to use the specific adaptors described by Correa in the cDNA synthesis methods described by Van Nostrand et al. One of ordinary skill in the art would have seen the disclosure of these sequences as suggesting that they are useful for performing the function of 3’- adaptor sequences in methods of constructing cDNA libraries.
For these reasons the invention taken as a whole is prima facie obvious.
Claims 4, 12, and 27 are rejected under 35 U.S.C. 103 as being unpatentable over Van Nostrand in view of Cao Bo as applied to claims 1, 2, 3, 5-11, 14-16, 19, 20, and 26 above, and further in view of Zarnegar et al. (Reference included with PTO-1449, additional supplementary figure 6 of record in previous action)
The disclosures of Van Nostrand and Cao Bo are discussed above. Van Nostrand in view of Cao Bo does not specifically disclose a method comprising removing a control portion from the sample after the RNA fragmentation step as described in claim 4. However, Zarnegar discloses a method for crosslinking and immunoprecipitation for measuring protein-RNA interactions. (abstract, also figure 1) As described in supplementary figure 6, the authors perform control experiments wherein “input” samples were quantitated from the lysate before immunoprecipitation. It would therefore have been obvious to one of ordinary skill in the art at the time of the invention to perform control measurements to measure the efficacy of a CLIP protocol as described by Van Nostrand. One of ordinary skill in the art would have found this to be obvious because Zarnegar shows that those of ordinary skill in the art perform such control measurements. Furthermore in doing so, one of ordinary skill in the art would have withdrawn a portion of the lysate after step (b) but before immunoprecipitation to serve as the input control, thereby infringing the limitations of claim 4.
Regarding claim 12, Zarnegar also describes the use of a dye-conjugated ligation adaptor for visualization of the complexes. (p. 2 first paragraph, p. 4 last paragraph) It would have been obvious to one of ordinary skill in the art at the time of the invention to use a dye-conjugated adaptor in the protocol described by Van Nostrand et al. One of ordinary skill in the art would have seen the disclosure of Zarnegar as suggesting that such a modification would be useful for the purpose of visualizing the ligated RNA. Regarding claim 27, the dye used by Zarnegar is IrDye®800CW, (p. 5 first paragraph) which according to the included certificate of analysis, (Included with PTO-892, downloaded from tocris.com) contains a cyanine structure. (see structure on p. 1 of certificate of analysis, part 1)
For these reasons the invention taken as a whole is prima facie obvious.
Claim 18 is rejected under 35 U.S.C. 103 as being unpatentable over Van Nostrand in view of Cao Bo as applied to claims 1, 2, 3, 5-11, 14-16, 19, 20, and 26 above, and further in view of Uddin et al. (Reference of record in previous action)
The disclosures of Van Nostrand and Cao Bo are discussed above. Van Nostrand in view of Cao Bo does not specifically disclose a method wherein the reverse transcription primer is biotinylated. However, Uddin et al. discloses that biotinylated primers can be used to produce biotinylated cDNA, which can then be purified by binding to streptavidin magnetic beads. (abstract, also figure 5) It would therefore have been obvious to one of ordinary skill in the art at the time of the invention to use a biotinylated reverse transcription primer in the protocol described by Van Nostrand et al. One of ordinary skill in the art would have seen the disclosure of Uddin as suggesting that such a modification would be useful for the purpose of purifying the resulting cDNA.
For these reasons the invention taken as a whole is prima facie obvious.
Claim 25 is rejected under 35 U.S.C. 103 as being unpatentable over Van Nostrand in view of Cao Bo as applied to claims 1, 2, 3, 5-11, 14-16, 19, 20, and 26 above, and further in view of Darnell et al. (US pre-grant publication 2014/0378316, cited in PTO-1449)
The disclosures of Van Nostrand and Cao Bo are discussed above. Van Nostrand in view of Cao Bo does not specifically disclose a using the disclosed method to screen small molecules for disruption of a RBP-RNA interaction. However, Darnell et al. describes a method for purifying a RNA molecule interacting with a RNA binding protein comprising the same general process of crosslinking a biological sample to create a RAN-RBP complex, cleaving the bound RNA, and detecting the fragments of RNA. (p. 1 paragraph 4) Darnell et al. further discloses that such methods can be used to screen molecules for their ability to disrupt a RBP-RNA interaction. (p. 1 paragraph 8) It would therefore have been obvious to one of ordinary skill in the art at the time of the invention to use the protocol described by Van Nostrand et al. for the purpose of screening small molecule disruption of RNA-RBP interactions. One of ordinary skill in the art would have found this to be obvious based on the disclosure by Darnell that such methods can be useful for this purpose.
For these reasons the invention taken as a whole is prima facie obvious.
Response to Arguments
Applicant’s arguments, submitted December 22, 2025, with respect to the above grounds of rejection, have been fully considered and not found to be persuasive to remove the rejections. Regarding the Rejection over Van Nostrand in view of Cao, Applicant argues that Van Nostrand does not describe a step of adding an exonuclease to remove free adaptor molecules. Furthermore with respect to the reference Cao Bo, Applicant argues that this reference serves a fundamentally different purpose than that of Van Nostrand and the present claims. Applicant argues that the method described by Cao Bo is directed to absolute quantitation of RNA, which necessitates uniform capture of all RNA species, and that the removal of excess linker as described therein would not be seen by one of ordinary skill in the art as useful to incorporate into a CLIP protocol as described by Van Nostrand. However, while it may be true that Cao Bo does not describe a CLIP protocol, both Van Nostrand and Cao Bo describe methods wherein the RNA is ultimately used to produce a cDNA library through reverse transcription. In both methods, the function of the 3’- adapter is to provide a template for reverse transcription. Therefore the disclosure by Cao Bo, that it is useful to remove the adapter described therein, would also be seen by one of ordinary skill in the art as suggesting that it would be useful to perform a similar step to remove unligated adapter in a CLIP method such as that described by Van Nostrand wherein the products were to be reverse transcribed to form a cDNA library.
It is further noted that the “DNA linkers” described by Cao Bo appears to refer to the same entity as the adapter described by Van Nostrand. See for example figures 1 and 2 of Cao Bo, wherein the “3’ linker” or “Linker1” are ligated to the 3’- end of the RNA wherein they then serve as templates for a reverse transcription primer. Therefore contrary to Applicant’s assertion, one of ordinary skill in the art would have reasonably considered these two methods to be equivalent.
Still further, Applicant argues that the present application defines two technical purposes for using an exonuclease as claimed, firstly to improve quality control using fluorescent primers and secondly to prevent the contamination of the resulting library by adaptor-derived artefacts. However, considering that both of the cited references also involve producing a cDNA library from the isolated RNA, it is unclear how the removal of the adapter/linker in Cao Bo’s method would not be for the prevention of adapter-derived artefacts in the resulting library. Regarding quality control using fluorescent adaptors, as written independent claim 1 does not use fluorescent adapters. Rather the claim merely refers to a generic “detection means” which is any chemical moiety detectable by any means, including native nucleic acids. Furthermore even regarding claims 12 and 27 which recite a fluorophore, even if the presence of the fluorophore was important to Applicant’s rationale for adding this step, a claim can be rendered obvious by references that suggest the same modification of the prior art but for a different purpose.
Regarding claims 4-6, Applicant further argues that the “agent which specifically interacts with protein side chains” in these claims does not refer to an antibody but rather to some other agent. However, as written the claims refer to the capture agent in very broad, functionally defined terms, and are not specific enough to exclude antibodies, which in fact interact with the side chains, albeit noncovalently, and contain carboxyl groups.
Applicant further describes claims 12, 13, and 18, Applicant points out the differences between these claims and the cited art. However, these arguments do not address the additional references cited to show obviousness of the additional elements.
Regarding claim 19, Applicant argues that the prior art does not describe using exonuclease II rather than exonuclease I. However, as presently written element (i) of claim 19 allegedly requiring the use of exonuclease III, is one of several different alternative provisos connected by “and/or,” indicating that only one of them must be true. Therefore there is no absolute requirement for the use of exonuclease III in this claim.
Applicant still further points to the declaration of Christopher Sibley under 37 CFR 1.132, which allegedly demonstrates the nonobviousness of the claimed invention. However, this declaration merely contains arguments by the declarant asserting that Cao Bo’s method is directed particularly toward absolute quantitation of RNA and that this means that the exonuclease digestion would not be applicable to a CLIP based method which does not quantitate all RNA in a sample. However, a review of Cao Bo’s method including figures 1 and 2 indicates that the adapter or linker used in this method is being attached as a template for reverse transcription, and the rationale for removing unligated adapter would be the same in any other method involving producing a cDNA library, such as Van Nostrand’s method. Still further, this indicates that regardless of the absence of such steps in previously published CLIP protocols, one of ordinary skill in the art would have recognized both the problem and the solution in the context of constructing a cDNA library.
For these reasons the rejections are deemed proper and made final.
The following new grounds of rejection are introduced:
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-3, 5-10, 14-15, 19, and 20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Masuda et al. (Foreign publication JP2019-017281, Reference and English machine translation included with PTO-892)
Independent claim 1 claims a process comprising steps of cross-linking a RNA molecule and a RNA-binding protein in a sample, contacting the sample with an agent that cleaves the crosslinked RNA to shorten said RNA, purifying the cross-linked complex, contacting the complex with an adaptor containing a detection means, removing unbound adaptor, isolating the adaptor-bound crosslinked complex, and visualizing said complex. Dependent claim 2 requires additional steps comprising partially digesting the RBP, purifying the RNA, and preparing it for high-throughput sequencing. Dependent claim 3 specifies the agent used to purify the RNB-RNA complex as being, for example, an antibody. Independent claim 5 describes a similar process further comprising steps of partially digesting the RNA binding protein, purifying the RNA, and preparing the RNA for high-throughput sequencing. Note that the term “detecting means” describing a portion of the adaptor, is generic to any molecular structure that could be detected by any method, including simply unmodified DNA or RNA that could be detected by hybridization or fluorescence, for example.
Masuda et al. discloses an improved method for analyzing a RNA-protein interaction from small amounts of sample. (p. 4 paragraphs 5-7) This method includes steps of crosslinking RNA and RNA-binding proteins in a cell using UV irradiation, lysing the cells, capturing the crosslinked complex on a bead using a target-specific antibody, treating the complex on the beads with an endonuclease, treating the complex on the beads with a 5’-3’ exonuclease, treating the complex with protease to release the RNA, recovering the RNA, and sequencing analysis. (pp. 4 paragraph 8, p. 5 lines 1-13) This process can also be carried out in a manner wherein the endonuclease treatment is performed before binding to the beads, (p. 9 lines 17-18) as is the case in the process of precent claim 1.
Furthermore in another embodiment Masuda et al. discloses ligating a linker onto the RNA before the step of exonuclease treatment. (p. 5 lines 20-22) In such an embodiment the 5’-3’ exonuclease is described as removing excess linker as well as nonspecific RNA remaining on the beads. (p. 6 lines 21-32) The RNA is then isolated and analyzed by high-throughput sequencing, which would involve, in the broadest reasonable sense, visualizing the RNA by a detection means. (The template sequence introduced in the linker)
With respect to claim 7, as discussed above, Masuda describes a cell lysis step.
Regarding claim 8, Masuda describes both UV crosslinking and RNA fragmentation with RNAse III. (p. 6 paragraph 9, p. 5 line 14)
Regarding claim 9, as described above, the beads used by Masuda would be considered to be a solid phase.
Regarding claim 10, p. 6 paragraph 9 of Masuda describes a washing step immediately after capturing the complexes on the beads.
Regarding claim 14, Masuda et al. discloses that the 3’- linker can be preadenylated. (p. 12 paragraph 24)
Regarding claim 19, Masuda et al. describes purification of the PCR products on a gel. (p. 8 lines 43-44)
Regarding claim 20, Masuda et al. discloses high-throughput sequencing of the resulting double stranded DNA. (Paragraph 9)
For these Masuda et al. anticipates the present claims.
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.
Claims 16 and 26 are rejected under 35 U.S.C. 103 as being unpatentable over Masuda et al. as applied to claims 1-3, 5-10, 14-15, 19, and 20 above, and further in view of Van Nostrand et al. (of record in previous action).
The disclosure of Masuda et al. is discussed above. Masuda et al. does not specifically describe the reverse transcription steps recited in claim 16. However, as discussed previously under 35 USC 103, Von Nostrand discloses a reverse transcription protocol comprising steps of reverse transcribing cDNA from the RNA,, digesting the primers with ExoSAP-IT, immobilization of the cDNA on silane beads, ligating a linker (primer) onto the bead, and performing PCR on the cDNA. (pp. 191-193, sections 3.9-3.11) It would have been obvious to one of ordinary skill in the art at the time of the invention to carry out the reverse transcription suggested by Masuda et al. using the steps described by Van Nostrand. Considering that Masuda describes their protocol as an improvement over prior art CLIP protocols such as Van Nostrand, and would therefore suggest to one of ordinary skill in the art using it for the same purposes as Van Nostrand’s protocol, including for example using the same reverse transcription and sequencing protocols to analyze the isolated RNA.
Regarding claim 26, Masuda does not describe using RNAse I as the endonuclease. However, Van Nostrand describes fragmenting the RNA using RNAse I. (p. 184 section 3.2.2) It would have been obvious to one of ordinary skill in the art at the time of the invention to use RNAse I in place of RNAse III in the method of Masuda. One of ordinary skill in the art would have found this to be obvious as Masuda and Van Nostrand describe these two enzymes as both being useful for fragmenting DNA in CLIP protocols, suggesting that they are equivalents usable for the same purpose.
Therefore the invention taken as a whole is prima facie obvious.
Claims 4, 12, and 27 are rejected under 35 U.S.C. 103 as being unpatentable over Masuda et al. as applied to claims 1-3, 5-10, 14-15, 19, and 20 above, and further in view of Zarnegar et al. (Reference included with PTO-1449, additional supplementary figure 6 of record in previous action)
The disclosure of Masuda is discussed above. Masuda does not specifically disclose a method comprising removing a control portion from the sample after the RNA fragmentation step as described in claim 4. However, Zarnegar discloses a method for crosslinking and immunoprecipitation for measuring protein-RNA interactions. (abstract, also figure 1) As described in supplementary figure 6, the authors perform control experiments wherein “input” samples were quantitated from the lysate before immunoprecipitation. It would therefore have been obvious to one of ordinary skill in the art at the time of the invention to perform control measurements to measure the efficacy of a CLIP protocol as described by Masuda. One of ordinary skill in the art would have found this to be obvious because Zarnegar shows that those of ordinary skill in the art perform such control measurements. Furthermore in doing so, one of ordinary skill in the art would have withdrawn a portion of the lysate after step (b) but before immunoprecipitation to serve as the input control, thereby infringing the limitations of claim 4.
Regarding claim 12, Zarnegar also describes the use of a dye-conjugated ligation adaptor for visualization of the complexes. (p. 2 first paragraph, p. 4 last paragraph) It would have been obvious to one of ordinary skill in the art at the time of the invention to use a dye-conjugated adaptor in the protocol described by Masuda et al. One of ordinary skill in the art would have seen the disclosure of Zarnegar as suggesting that such a modification would be useful for the purpose of visualizing the ligated RNA. Regarding claim 27, the dye used by Zarnegar is IrDye®800CW, (p. 5 first paragraph) which according to the included certificate of analysis, (Included with PTO-892, downloaded from tocris.com) contains a cyanine structure. (see structure on p. 1 of certificate of analysis, part 1)
For these reasons the invention taken as a whole is prima facie obvious.
Claim 18 is rejected under 35 U.S.C. 103 as being unpatentable over Masuda as applied to claims 1-3, 5-10, 14-15, 19, and 20 above, and further in view of Uddin et al. (Reference of record in previous action)
The disclosure of Masuda is discussed above. Masuda does not specifically disclose a method wherein the reverse transcription primer is biotinylated. However, Uddin et al. discloses that biotinylated primers can be used to produce biotinylated cDNA, which can then be purified by binding to streptavidin magnetic beads. (abstract, also figure 5) It would therefore have been obvious to one of ordinary skill in the art at the time of the invention to use a biotinylated reverse transcription primer in the protocol described by Masuda et al. One of ordinary skill in the art would have seen the disclosure of Uddin as suggesting that such a modification would be useful for the purpose of purifying the resulting cDNA.
For these reasons the invention taken as a whole is prima facie obvious.
Claim 25 is rejected under 35 U.S.C. 103 as being unpatentable over Masuda as applied to claims 1-3, 5-10, 14-15, 19, and 20 above, and further in view of Darnell et al. (US pre-grant publication 2014/0378316, cited in PTO-1449)
The disclosure of Masuda is discussed above. Masuda does not specifically disclose a using the disclosed method to screen small molecules for disruption of a RBP-RNA interaction. However, Darnell et al. describes a method for purifying a RNA molecule interacting with a RNA binding protein comprising the same general process of crosslinking a biological sample to create a RAN-RBP complex, cleaving the bound RNA, and detecting the fragments of RNA. (p. 1 paragraph 4) Darnell et al. further discloses that such methods can be used to screen molecules for their ability to disrupt a RBP-RNA interaction. (p. 1 paragraph 8) It would therefore have been obvious to one of ordinary skill in the art at the time of the invention to use the protocol described by Van Nostrand et al. for the purpose of screening small molecule disruption of RNA-RBP interactions. One of ordinary skill in the art would have found this to be obvious based on the disclosure by Darnell that such methods can be useful for this purpose.
For these reasons the invention taken as a whole is prima facie obvious.
Claim 28 is rejected under 35 U.S.C. 103 as being unpatentable over Masuda as applied to claims 1-3, 5-10, 14-15, 19, and 20 above, and further in view of Oganesian et al. (Reference included with PTO-892)
The disclosure of Masuda is discussed above. Masuda does not specifically disclose an embodiment wherein the exonuclease is RecJf. However Oganesian et al. discloses that RecJf is a 5’-3’ exonuclease that can be sued to digest single-stranded RNA. It would therefore have been obvious to one of ordinary skill in the art at the time of the invention to use RecJf as the exonuclease in the method described by Masuda, in view of the fact that Oganesian et al. discloses that it is an exonuclease performing the same function as the exonuclease described by Masuda.
For these reasons the invention taken as a whole is prima facie obvious.
Claim 28 is rejected under 35 U.S.C. 103 as being unpatentable over Van Nostrand in view of Cao Bo as applied to claims 1, 2, 3, 5-11, 14-16, 19, 20, and 26 above, and further in view of Oganesian et al. (Reference included with PTO-892)
The disclosures of Van Nostrand and Cao Bo are discussed above. Van Nostrand in view of Cao Bo does not specifically disclose an embodiment wherein the exonuclease is RecJf. However Oganesian et al. discloses that RecJf is a 5’-3’ exonuclease that can be sued to digest single-stranded RNA. It would therefore have been obvious to one of ordinary skill in the art at the time of the invention to use RecJf as the exonuclease in the method described by Van Nostrand in view of Cao Bo, in view of the fact that Oganesian et al. discloses that it is an exonuclease performing the same function as the RecJ exonuclease described by Cao Bo.
For these reasons the invention taken as a whole is prima facie obvious.
Conclusion
No claims are allowed in this action.
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/ANDREA OLSON/ Primary Examiner, Art Unit 1693 2/10/2025