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 .
Application Status and Election
Claims 1-20 are pending.
Applicant’s election without traverse of Group I, encompassing claims 1-10 and 14-20 in the reply filed October 10, 2025 is acknowledged. Claims 11-13 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected group, there being no allowable generic or linking claim.
Applicant’s election of PafA as the proximity tagging enzyme, dLwCas13a as the Cas13 enzyme and LoxP as the promoter in the reply filed on October 10, 2025 is also acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the species restriction requirement, the species election has been treated as an election without traverse (MPEP § 818.01(a)). It is noted that neither the elected “promoter” LoxP or the other species in claims 10 (UAS) are actually promoters (See paragraph 18 below). Inducible promoters are recited in [0064] of the specification. Based on the search for possible inducible promoters it appears that inducible promoters are obvious variants of each other. For that reason, the species restriction directed to inducible promoters is withdrawn. Claim 4 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim.
Claims 1-3, 5-10 and 14-20 are under examination.
Priority
Acknowledgment is made of applicant's claim for foreign priority based on a PCT application filed in China on February 25, 2020 – Application PCT/CN2020/076562. It is noted, however, that applicant has not filed a certified copy of the PCT/CN2020/076562 application as required by 37 CFR 1.55 and no access code has been provided to allow retrieval of the application.
As such the effective filing date of the claimed invention is February 24, 2021, the date the PCT/CN2021/077602 application was filed.
Drawings
The drawings are objected to because the lines, shadings, numbers and letters of FIGs 1, 2B-D, 3A-E, 4A-C, 5, 6, 7, 8A-B, 10A-B, 11A-D (graph labels) are not sufficient to provide satisfactory reproduction characteristics. 37 CFR 1.84(l) states that “all drawings must be made by a process which will give them satisfactory reproduction characteristics. Every line, number, and letter must be durable, clean, black (except for color drawings), sufficiently dense and dark, and uniformly thick and well-defined.” In the instant case, the text in the indicated FIGs is light grey or otherwise not sufficiently dense and dark to permit satisfactory reproduction characteristics; the letters over shading especially in FIGs 1-3 and 6 are not sufficiently dark for reproduction; the text in the indicated FIGs is very small, blurry and/or of poor resolution.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
The use of the terms Lipofectamine®, Hyclone®, ClonExpress®, Mut Express®, NanoDrop®, MicroElute®, which are trade name or marks used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Nucleotide and/or Amino Acid Sequence Disclosures
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter “Legal Framework”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
This application contains sequence disclosures in accordance with the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR 1.831(a) and 1.831(b). However, this application fails to comply with the requirements of 37 CFR 1.831-1.834. The examiner has noted that two nucleotide sequences on page 26 of the Specification are not labeled with SEQ ID NOs and do not appear to be in the sequence listing. Applicant must provide:
• A replacement “Sequence Listing XML” part of the disclosure, as described above in item 1. or 2., as well as
• A statement that identifies the location of all additions, deletions, or replacements of sequence information in the “Sequence Listing XML” as required by 1.835(b)(3);
• A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.835(b)(4);
• A statement that the “Sequence Listing XML” includes no new matter in accordance with 1.835(b)(5); and
• A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required incorporation by reference paragraph as required by 37 CFR 1.835(b)(2), consisting of:
o A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
o A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Claim Objections
Claims 6 and 16 are objected to because of the following informalities:
Claims 6 and 16 recite a series of Cas13 proteins. In lines 5, 7 and 8, after LspCas13a, Pin3Cas13b, and AspCas13c, respectively, there is an extra comma and an extra space, which should be deleted. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 8, 10 and 18 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.
Claims 8 and 18 recite “wherein the Cas13 is dLwCas13a with an R474A or R1046A mutation. The claims are indefinite because there is no SEQ ID NO in reference to the amino acid positions. Although wildtype LwCas13a has an arginine at positions 474 and 1046 (See Genbank WP_021746774.1, https://www.ncbi.nlm.nih.gov/protein/WP_021746774.1, [retrieved 12/16/2025]), dLwCas13a comprises a genus of proteins that can have various amino acid additions or deletions that can alter the amino acid position numbering. For instance, SEQ ID NO 12, which the Specification teaches is dLwaCas13a-PafA-P2A-EGFP (pages 21-22), does not comprise an arginine or alanine at positions 474 or 1046. As such it is not clear which arginine should be substituted with alanine in the dLwCas13a protein.
To remedy the indefiniteness, it is suggested that claims 8 and 18 recite “wherein the Cas13 is dLwCas13a comprising an arginine to alanine substitution in one or more HEPN domains.” Alternatively, the claims can recite specific amino acid substitutions in reference to a SEQ ID NO.
Claim 10 recites “wherein the inducible promoter is LoxP or UAS”. Claim 10 is confusing because LoxP isn’t a promoter, and while UAS can be a component of promoters, it is not a promoter in and of itself. The specification teaches that LoxP is a sequence that is recognized by the CRE recombinase to excise the sequence between two LoxP sites ([0066], [0092]). This is consistent with the use of “LoxP” in the art. See e.g., Cre-Lox Recombination, https://info.abmgood.com/cre-lox-recombination-introduction [retrieved 12/17/2025]). Nowhere in the Specification is LoxP listed as a promoter. UAS stands for “Upstream Activatable Element” and is an upstream enhancer element to a core promoter that binds to the GAL4 transcription factor (Addgene Blogpost: Controlling Gene Expression in Flies with Gal4/UAS, https://blog.addgene.org/quick-guide-to-working-with-drosophila-part-2-controlling-gene-expression-in-flies-with-gal4/uas, posted July 21, 2017, [retrieved 12/16/2025]). UAS is only part of an inducible promoter by the fact that expression of its GAL4-binding partner can be under the control of an inducible promoter. As such, it is confusing to recite that “the inducible promoter is LoxP or UAS” as it’s not clear what limitations are required, if any, on the promoter induction.
Claim Rejections - 35 USC § 102 - Lin
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 14-17 and 19 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Lin (Lin et al., In vivo discovery of RNA proximal proteins in human cells via proximity-dependent biotinylation. bioRxiv preprint doi: https://doi.org/10.1101/2020.02.28.970442, posted October 8, 2020).
As indicated above in paragraph 7, the effective filing date of the claimed invention is February 24, 2021. As such, Lin is prior art under §102(a)(1).
Regarding claims 14-17, Lin teaches dPspCas13b (i.e., a catalytically dead PspCas13b) fused to APEX2 (Fig 1A-B). Lin teaches APEX2 tags nearby proteins with biotin (i.e., APEX2 is a proximity tagging enzyme) (Fig 1A).
Regarding claim 19, Lin teaches APEX2 is an ascorbate peroxidase (Abstract).
Claim Rejections - 35 USC § 102 - Han
Claims 14-17 and 19-20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Han (Han et al., PNAS (2020), 117: 22068-22079, published August 24, 2020).
As indicated above in paragraph 7, the effective filing date of the claimed invention is February 24, 2021. As such, Han is prior art under §102(a)(1).
Regarding claims 14-17, Han teaches dRfxCas13d (i.e., a catalytically dead RfxCas13d) fused to APEX2 (Fig 1A and 2C). Han teaches APEX2 tags nearby proteins with biotin (i.e., APEX2 is a proximity tagging enzyme) (Fig 1A).
Regarding claim 19, Han teaches APEX2 is a peroxidase and uses ascorbate as a substrate (i.e., APEX2 is an ascorbate peroxidase) (Abstract).
Regarding claim 20, Han teaches the dRfxCas13d-APEX2 fusion protein also comprises an NLS (Fig 2C).
Claim Rejections - 35 USC § 102 - Zhang
Claims 14-20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Zhang (Zhang et al., Nucleic Acids Research (2020), 48: e52, pages 1-8, published March 6, 2020).
As indicated above in paragraph 7, the effective filing date of the claimed invention is February 24, 2021. The applied reference has four common authors with the instant application, but names two additional authors. Zhang is prior art under §102(a)(1).
Regarding claims 14-17, Zhang teaches dLwaCas13a (i.e., a catalytically dead LwaCas13a) fused to PafA (Fig 1A-B). Zhang teaches PafA tags nearby proteins with PupE (i.e., PafA is a proximity tagging enzyme (Fig 1A).
Regarding claim 18, Zhang teaches the dLwaCas13a has an R474A and R1046A substitutions (page 2, ¶3).
Regarding claim 19, Zhang teaches PafA is a Pup ligase (page 2, ¶1).
Regarding claim 20, Zhang teaches the dLwaCas13a-PafA fusion protein also comprised an NLS (page 4, ¶3).
Claim Rejections - 35 USC § 102 - Hsu
Claims 14-17 and 19 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Hsu (US 20190169595 A1, published June 6, 2019).
Regarding claims 14-15 and 19, Hsu teaches Cas13d fused to biotin ligase or peroxidase (i.e., a fusion protein comprising Cas13d and a proximity tagging enzyme) ([0485]).
Regarding claim 16, Hsu teaches the Cas13d fusion is from Eubacterium siraeum (i.e., is EsCas13d) ([0026], [0042]; FIGs 2-3).
Regarding claim 17, Hsu teaches fusing catalytically inactive Cas13d to biotin ligase ([0388]).
Claim Rejections - 35 USC § 103 - Hsu
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.
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.
Claims 1-2, 5-7, 9-10 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Hsu (US 20190169595 A1, published June 6, 2019).
The teachings of Hsu are recited above in the rejections of claims 14-17 and 19 and incorporated here. Regarding claims 1-2 and 5-7, Hsu also teaches cells and host organisms comprising expression vectors encoding Cas13d proteins (i.e., a transgenic organism comprising a recombinant polynucleotide encoding the Cas13d protein) ([0407]). Regarding claims 9-10, claim 10 is indefinite for the reasons described above in paragraph 18. For the purpose of examination, claim 10 is interpreted as encompassing any inducible promoter. Hsu teaches expressing Cas13d from inducible promoters in cells (0411]). Regarding claim 20, Hsu teaches Cas13d-effector domain fusions can also be fused to a nuclear localization sequence (NLS) ([0387], [0504], [0534]).
Hsu does not teach in a single embodiment a Cas13d-biotin ligase fusion expressed from a polynucleotide in cells, or under the control of an inducible promoter, or fused to an NLS.
Regarding claims 1-2, 5-7 and 9-10, it would have been obvious to one skilled in the art before the effective filing date of the claimed invention to have expressed Cas13d-biotin ligase fusion from an inducible promoter in cells in an organism. It would have amounted to using known means to express a known fusion protein in cells to yield predictable results. The skilled artisan would have predicted the polynucleotides could be delivered to cells because Hsu teaches that Cas13d can be expressed in cells and from inducible promoters. The skilled artisan would have been motivated to do so to label and detect RNA binding proteins that interact with the targeted RNA in cells. One would have specifically been motivated to use an inducible promoter to prevent unwanted Cas13d-biotin ligase labeling in cells during transgenic cell selection.
Regarding claim 20, it would have also been obvious to one skilled in the art to have included an NLS fused to the Cas13d-biotin ligase fusion protein. It would have amounted to the simple combination of known elements by known means to yield predictable results. The skilled artisan would have predicted that an NLS could be included because Hsu demonstrates NLS included on other Cas13d-fusion proteins. One would have been motivated to do so for the purpose of labeling nuclear RNA-binding proteins that interact with the targeted nuclear RNAs.
Claim Rejections - 35 USC § 103 - Zhang
Claims 1-2, 5-10, 14-20 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang (US 20190359971 A1, published November 28, 2019, priority to at least June 19, 2017). Claims 6 and 16 are evidenced by Genbank (WP_021746774.1, https://www.ncbi.nlm.nih.gov/protein/WP_021746774.1, [retrieved 12/16/2025]). This rejection also addresses the elected Cas13a, dLwaCas13a.
For logistical purposes, the rejections of claims directed to fusion proteins (14-20) are recited first followed by the rejections of claims directed to cells comprising the fusions proteins (1-2, 5-10).
Regarding claims 14-15, 17 and 19, Zhang teaches “The ability of dC2c2 (dCas13a) to bind to specified sequences could be used… to… (iv) capture specific transcripts (… use of dC2c2 to localize biotin ligase activity [a proximity tagging enzyme] to transcripts) to enrich for proximal molecular partners including RNAs and proteins” (i.e., the Cas13a is catalytically dead and recruits biotin ligase to the targeted RNA) ([0015]). Zhang teaches RNA-binding proteins can be identified using an RNA-targeting effector protein of the invention (i.e., dC2c2 or dCas13a) to label locally bound proteins with biotin ([0291]). Zhang also teaches dC2c2/dCas13a fused to a variety of effector proteins in order to localize the effector protein at targeted RNA ([0305], [0513]).
Zhang does not expressly teach that the biotin ligase is fused to dC2c2/dCas13a for recruitment.
It would have been obvious to one skilled in the art before the effective filing date of the claimed invention to have fused the biotin ligase to dCas13a. It would have amounted to the simple combination of known elements to yield predictable results. The skilled artisan would have predicted that the biotin ligase could actually be fused dCas13a because Zhang teaches many other effector domains fused to dCas13a for the purpose of recruiting the effector to the target RNA. The skilled artisan would have been motivated to do so because Zhang teaches protein fusions as a means for effector domain recruitment to a target RNA.
Regarding claim 16, the Specification identifies LwaCas13a as WP_021746774.1 (Table B). Genbank teaches that accession WP_021746774.1 is Cas13a originating from Letotrichia wadei and was originally named C2c2. Thus, the dC2c2 taught in Zhang is inherently dLwaCas13a.
Regarding claim 18, dC2c2 was generated by making R474A and R1046A substitutions ([1028]).
Regarding claim 20, Zhang also teaches an NLS fused to catalytically inactive Cas13a that is also fused to an effector domain ([0126], [0047], Fig 45).
It would have also been obvious to one skilled in the art to have included an NLS fused to the Cas13a-biotin ligase fusion protein rendered obvious for claim 14. It would have amounted to the simple combination of elements by known means to yield predictable results. The skilled artisan would have predicted that an NLS could be included because Zhang demonstrates an NLS included on other Cas13a-fusion proteins. One would have been motivated to do so for the purpose of labeling nuclear RNA-binding proteins that interact with the targeted nuclear RNAs.
Regarding claims 1-2 and 5-8, the teachings of Zhang regarding dCas13a and biotin ligase and the obviousness of fusing the two domains together are recited above as for claims 14-19 and incorporated here. Zhang teaches recombinant expression vectors comprising polynucleotides encoding the Cas13a proteins for expression in host cells ([0163]-[0164], [0740]). Zhang teaches expressing the Cas13a proteins in mammalian tissues, organs and organisms (i.e., a transgenic organism).
It would have been obvious to one skilled in the art to have introduced an expression vector encoding the obvious dCas13a-biotin ligase into a host cell and organism taught in Zhang. It would have amounted to the simple combination of known elements by known means to yield predictable results. The skilled artisan would have predicted that a dCas13a-biotin ligase could be encoded on a polynucleotide and introduced into cells of an organism because both dCas13a and biotin ligase are proteins and therefore can be genetically encoded. Additionally, Zhang teaches encoding dCas13a fusion proteins in polynucleotides and introducing the expression vectors into cells. The skilled artisan would have been motivated to do so in order to determine proteins that bind to RNAs normally in different cell types and under different conditions.
Regarding claims 9-10, claim 10 is indefinite for the reasons described above in paragraph 18. For the purpose of examination, claim 10 is interpreted as encompassing any inducible promoter. Zhang teaches expression of Cas13a effectors can be modulated using inducible promoters that are known in the art ([0302], [0349], [0706]).
It would have been obvious to one skilled in the art before the effective filing date of the claimed invention to have expressed Cas13d-biotin ligase fusion from an inducible promoter in cells in an organism. It would have amounted to using known means to express a known fusion protein in cells to yield predictable results. The skilled artisan would have predicted the polynucleotides could be expressed using inducible promoters because Zhang teaches such genetic inducible systems are well-known in the art. One would have specifically been motivated to use an inducible promoter to prevent unwanted Cas13a-biotin ligase labeling in cells during transgenic cell selection.
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Zhang (US 20190359971 A1, published November 28, 2019, priority to at least June 19, 2017), as applied to claims 1-2, 5-10, 14-20 above, and further in view of Liu (Liu et al., Nature Methods (2018), 15: 715-722). This rejection also addresses the elected tagging enzyme PafA.
The teachings of Zhang are recited above and applied as for claims 1-2, 5-10, and 14-20. Zhang also teaches proximity labeling technology employs an affinity tag to label polypeptides and RNAs in the vicinity of a protein or RNA of interest ([0278]). Zhang teaches the RNA targeting effector protein (i.e., dCas13a) can be used to target to label a molecule of interest ([0278]). Zhang teaches such technologies include Apex labeling ([0277]-[0278]) and can use biotin ligase ([0291]).
Zhang does not teach the proximity tagging enzyme is PafA.
Liu teaches a proximity-based tagging system called PUP-IT, in which a small protein tag called Pup (prokaryotic ubiquitin protein) is ligated onto nearby proteins by the PafA enzyme (Abstract; Fig 1). Liu teaches fusing PafA to a “bait” protein of interest to determine protein binding partners (Fig 1). Liu demonstrates fusion of PafA to CD28 (Fig 3), FRB (Fig 5) and IL-2 (Fig 6). Liu teaches developing their working model of the PUP-IT system with membrane proteins, but notes that applications of PUP-IT are not limited to membrane proteins (page 720, ¶2). Liu teaches the PUP-IT system is an alternative to the APEX and BioID system that label nearby substrates/proteins with biotin using a peroxidase enzyme or biotin ligase, respectively, fused to the protein of interest (page 715, ¶3 and page 720, ¶3). Liu teaches that PUP-IT appears to be more active than BioID in cells (page 720, ¶4). Liu describes the PUP-IT system as “complementary” to the APEX and BioID proximity labeling systems (page 720, ¶3).
It would have been obvious to one skilled in the art before the effective filing date of the claimed invention to have substituted the biotin ligase enzyme for Liu’s PafA enzyme in the dCas13a fusion protein rendered obvious for claim 1. It would have amounted to substituting one known proximity tagging enzyme for another by known means to yield predictable results. The skilled artisan would have predicted that PafA could be fused to dCas13a because 1) Zhang teaches a large variety of different domains fused to dCas13a and 2) Liu demonstrates PafA fused to at least three different cellular proteins. Because the prior art recognizes the equivalence of PafA and biotin ligase for the purpose of proximity tagging of proteins, an express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. MPEP 2144.06.II. Nevertheless, the skilled artisan would have been motivated to make the substitution because Liu teaches that PafA is more active in cells than the biotin ligase of the BioID system.
Conclusion
No claims are allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CATHERINE KONOPKA whose telephone number is (571)272-0330. The examiner can normally be reached Mon - Fri 7- 4.
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/CATHERINE KONOPKA/Examiner, Art Unit 1635