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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on March 16th, 2026 has been entered.
Response to Amendment
The amendment filed March 16th, 2026 is acknowledged. Regarding the Office Action mailed December 17th, 2025:
The objections to the claims are withdrawn in view of the amendments.
The rejections set forth under 35 U.S.C. 102(a)(2) are withdrawn in view of the joint research agreement now disclosed as a part of the specification.
The rejections set forth under 35 U.S.C. 103 in relation to Abudayyeh (US20180274017A1, effectively filed in March 2017) and US11104937B2, also effectively filed in March 2017, are withdrawn in view of the joint research agreement now disclosed as a part of the specification. The rejections set forth under 35 U.S.C. 103 in relation to Gootenberg and combinations with Gootenberg are withdrawn in view of the declaration under 37 CFR 1.130(a) disqualifying the reference (see below).
The double patenting rejection set forth in relation to Gootenberg and combinations with Gootenberg are withdrawn in view of the declaration under 37 CFR 1.130(a) disqualifying the reference (see below).
Maintained, modified, or new rejections are set forth below, as necessitated by the amendments. Responses to arguments, if necessary, follow their respective rejection sections.
Claim Summary
Claim 1 has been amended. Claims 6-9, 11, 14-15, 18, 21-24, 26, 30, 32, 34, 36, 38, 41-42, 44, 48, 50, 52-53, 55, 57-58, 60-61, 63-65, 67-68, and 73-75 have been canceled. Claim 76 has been added. Claims 1-5, 10, 12-13, 16-17, 19-20, 25, 27-29, 31, 33, 35, 37, 39-40, 43, 45-47, 49, 51, 54, 56, 59, 62, 66, 69-72, and 76 are pending. Claims 45-47, 49, 51, 54, 56, 59, 62, and 66 are withdrawn from consideration as being drawn to a non-elected invention/species. Claims 1-5, 10, 12-13, 16-17, 19-20, 25, 27-29, 31, 33, 35, 37, 39-40, 43, 69-72, and 76 are under examination and discussed in this Office action.
Claim Interpretation – Modified – Necessitated by Amendment
Claim 1 recites “a nucleic acid detection system comprising: one or more guide RNAs designed to base-pair to a complementary target nucleotide sequence of a target molecule, a Type VI CRISPR-Cas RNA targeting effector protein or a homolog, an ortholog, or a functional variant thereof, wherein complex formation between the CRISPR-Cas effector protein and the one or more guide RNAs annealed to the target nucleotide sequence triggers a non-specific collateral ribonuclease activity; and an RNA-based masking construct comprising an RNA aptamer having a quadruplex with enzymatic activity that produces a color signal, wherein inactivation of the enzymatic activity of the quadruplex by the effector protein's non-specific collateral ribonuclease activity results in an irreversible elimination of the color signal, such that the elimination of the color signal indicates the presence of the target molecule”.
Claims 1-5, 10, 12-13, 16-17, 19-20, 25, 27-29, 31, 33, 35, 37, 39-40, 43, 69-72, and 76 appear to recite a system (apparatus) with functional limitations and intended results when performed in a method step. MPEP 2114 states “[W]hile features of an apparatus may be recited either structurally or functionally, claims directed to an apparatus must be distinguished from the prior art in terms of structure rather than function. >In re Schreiber, 128 F.3d 1473, 1477-78, 44 USPQ2d 1429, 1431-32 (Fed. Cir. 1997) (The absence of a disclosure in a prior art reference relating to function did not defeat the Board’s finding of anticipation of claimed apparatus because the limitations at issue were found to be inherent in the prior art reference); see also In re Swinehart, 439 F.2d 210, 212-13, 169 USPQ 226, 228-29 (CCPA 1971); In re Danly, 263 F.2d 844, 847, 120 USPQ 528, 531 (CCPA 1959). “[A]pparatus claims cover what a device is, not what a device does.” Hewlett-Packard Co. v. Bausch & Lomb Inc., 909 F.2d 1464, 1469, 15 USPQ2d 1525, 1528 (Fed. Cir. 1990).”
Claim Rejections - 35 USC § 112(d) – Maintained
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 69 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends. Claim 69 recites the limitation “wherein the elimination of the color signal comprises an elimination of the color signal produced by the RNA aptamer”. Claim 1 recites the limitation “an RNA-based masking construct comprising an RNA aptamer having a quadruplex with enzymatic activity that produces a color signal, wherein inactivation of the enzymatic activity of the quadruplex by the effector protein's non-specific collateral ribonuclease activity results in an irreversible elimination of the color signal, such that the elimination of the color signal indicates the presence of the target molecule”. Based on the language of claim 1, it has already been claimed that elimination of the color signal comprises an elimination of the color signal produced by the RNA aptamer. This is because the RNA aptamer has a quadruplex with enzymatic activity that produces a color signal, and inactivation of the enzymatic activity of the quadruplex results in elimination of the color signal. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Response to Arguments
Applicant's arguments filed March 16th, 2026 have been fully considered but they are not persuasive.
The Applicant states that the rejection does not apply to the claim as presently presented (Page 14 of the Remarks filed March 16th, 2026), with no further evidence presented of how it does not apply. Therefore, the argument is not found persuasive and the rejection is maintained.
Claim Rejections - 35 USC § 103 - New - Necessitated by Further Consideration
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.
Claims 1-4, 10, 12-13, 17, 19, 39, and 69-72 are rejected under 35 U.S.C. 103 as being unpatentable over Nie (CN107557455A; original text provided with translation), in view of Travascio (A ribozyme and a catalytic DNA with peroxidase activity: active sites versus cofactor-binding sites, Cell Chemical Biology, November 1999, 6, 779-787; previously cited), and as evidenced by New England Biolabs (FAQ: What is the promoter sequence of T7 RNA Polymerase? [online]. New England Biolabs, [2015] [retrieved on July 7th, 2025]. Retrieved from: https://www.neb.com/en-us/faqs/2015/01/30/what-is-the-promoter-sequence-of-t7-rna-polymerase?; previously cited) and East-Seletsky (RNA targeting by functionally orthogonal Type VI-A CRISPR-Cas enzymes, Molecular Cell, May 2017, 66, 373-383; cited on the IDS filed January 10th, 2024; previously cited).
Regarding instant claim 1, Nie teaches a nucleic acid detection system comprising: one or more guide RNAs designed to base-pair to a complementary target nucleotide sequence of a target molecule (Page 16, paragraph [0021]; Pages 19, paragraph [0026]), a Type VI CRISPR-Cas RNA targeting effector protein (Page 16, paragraph [0021]; Pages 16-17, paragraph [0022]), wherein complex formation between the CRISPR-Cas effector protein and the one or more guide RNAs annealed to the target nucleotide sequence triggers a non-specific collateral ribonuclease activity (Pages 20-21, paragraph [0028]; Page 25, paragraph [0034]). Nie further teaches an RNA-based masking construct that can be cleaved by the collateral ribonuclease activity (Pages 20-21, paragraph [0028]; Page 25, paragraph [0034]).
Nie does not teach an RNA-based masking construct comprising an RNA aptamer having a quadruplex with enzymatic activity that produces a color signal, wherein inactivation of the enzymatic activity of the quadruplex by the effector protein's non-specific collateral ribonuclease activity results in an irreversible elimination of the color signal, such that the elimination of the color signal indicates the presence of the target molecule.
Travascio, in a reasonably pertinent field, teaches an RNA aptamer having a quadruplex with enzymatic activity that produces a color signal (Page 780, columns 1 and 2, first paragraph in each column; Figure 1A).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the RNA masking construct of Nie with the RNA aptamer quadruplex of Travascio. Since Travascio teaches RNA aptamer quadruplexes, which is reasonably pertinent to the ribonuclease activity of the Type VI CRISPR-Cas RNA targeting effector protein of Nie, one of ordinary skill in the art would combine the two teachings with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to make this modification because the RNA aptamer quadruplex binds hemin and exhibits a peroxidase activity superior to that of some Fe(III)-hemoproteins (Page 785, column 2, paragraph 2).
It is noted that the subject matter of a properly construed claim is defined by the terms that limit its scope. It is this subject matter that must be examined. As a general matter, the grammar and intended meaning of terms used in a claim will dictate whether the language limits the claim scope. Language that suggests or makes optional but does not require steps to be performed or does not limit a claim to a particular structure does not limit the scope of a claim or claim limitation. “Wherein” clauses are examples of language that may raise a question as to the limiting effect of the language in a claim. See MPEP 2103 I.C. and MPEP § 2111.04. The wherein clause directed to “inactivation of the enzymatic activity of the quadruplex by the effector protein's non-specific collateral ribonuclease activity results in an irreversible elimination of the color signal, such that the elimination of the color signal indicates the presence of the target molecule” represents an intended use of the system if it were to be used in a method. Furthermore, the wherein clause claims what can be reasonably considered as innate properties of the RNA-based masking construct comprising an RNA aptamer having a quadruplex with enzymatic activity that produces a color signal because the masking construct contains all the purported structural components needed to perform the wherein clause. For these reasons, it does not add further weight to the structure of the system.
Regarding instant claim 2, Nie, in view of Travascio, teaches the system of claim 1. Travascio further teaches wherein the enzymatic activity comprises peroxidase activity (Page 781, column 2, paragraph 2; Figure 2).
Regarding instant claim 3, Nie, in view of Travascio, teaches the system of claim 1. Nie further teaches the system further comprising nucleic acid amplification reagents (Page 11, paragraph [0013]).
Regarding instant claim 4, Nie, in view of Travascio, teaches the system of claim 1. Nie further teaches the system further comprising a primer with a nucleotide sequence of an RNA polymerase promoter sequence, wherein the primer can anneal to a nucleotide sequence of the target molecule (Page 12, paragraph [0014]; Page 13, paragraph [0015]). As evidenced by New England Biolabs, T7 is an RNA polymerase (Page 1).
Regarding instant claim 10, Nie, in view of Travascio, teaches the system of claim 5. East-Seletsky further teaches wherein the RNA-targeting effector protein is C2c2 (Pages 16-17, paragraph [0022]). As evidenced by East-Seletsky, Cas13a proteins used to be called C2c2 (Page 373, Summary).
Regarding instant claim 12, Nie, in view of Travascio, teaches the system of claim 10. Nie further teaches wherein the C2c2 is within 20 kb of a Cas 1 gene (Pages 16-17, paragraph [0022]).
It is noted that the subject matter of a properly construed claim is defined by the terms that limit its scope. It is this subject matter that must be examined. As a general matter, the grammar and intended meaning of terms used in a claim will dictate whether the language limits the claim scope. Language that suggests or makes optional but does not require steps to be performed or does not limit a claim to a particular structure does not limit the scope of a claim or claim limitation. “Wherein” clauses are examples of language that may raise a question as to the limiting effect of the language in a claim. See MPEP 2103 I.C. and MPEP § 2111.04. The wherein clause directed to “the C2c2 is within 20 kb of a Cas 1 gene” does not limit the C2c2 protein of the claimed system to a particular structure beyond what has already been taught by Nie and therefore does not add further weight to the structure of the system.
Regarding instant claim 13, Nie, in view of Travascio, teaches that system of claim 12. Nie further teaches wherein the C2c2 effector protein is from an organism of the genus Leptotrichia; optionally, wherein the C2c2 effector protein is from the organism Leptotrichia wadei (Pages 16-17, paragraph [0022]).
Regarding instant claim 17, Nie, in view of Travascio, teaches the system according to claim 1. Nie further teaches wherein the one or more guide RNAs comprise a mismatch between a nucleotide of said guide sequence and a nucleotide of the target nucleotide sequence (Page 20, paragraph [0027]; Pages 33-34, paragraph [0048]), and wherein said mismatch is optionally up- or downstream of a single-nucleotide polymorphism (SNP) or other single nucleotide variation in said target molecule's nucleotide sequence (Page 20, paragraph [0027]).
Regarding instant claim 19, Nie, in view of Travascio, teaches the system of claim 1. Nie further teaches wherein the one or more guide RNAs are designed to detect a single nucleotide polymorphism in the target molecule, or a splice variant of an RNA transcript (Page 20, paragraph [0027]).
Regarding instant claim 39, Nie, in view of Travascio, teaches the system of claim 3. Nie further teaches wherein the nucleic acid amplification reagents are reagents to amplify target RNA molecules using a nucleic acid amplification technique, and where the nucleic acid amplification technique comprises recombinase polymerase amplification (RPA) (Page 11, paragraphs [0012]-[0013]).
Regarding instant claim 69, Nie, in view of Travascio, teaches the system of claim 1. Travascio further teaches an RNA aptamer having a quadruplex with enzymatic activity that produces a color signal (Page 780, columns 1 and 2, first paragraph in each column; Figure 1A), which can innately perform wherein the elimination of the color signal comprises an elimination of the color signal produced by the RNA aptamer.
It is noted that the subject matter of a properly construed claim is defined by the terms that limit its scope. It is this subject matter that must be examined. As a general matter, the grammar and intended meaning of terms used in a claim will dictate whether the language limits the claim scope. Language that suggests or makes optional but does not require steps to be performed or does not limit a claim to a particular structure does not limit the scope of a claim or claim limitation. “Wherein” clauses are examples of language that may raise a question as to the limiting effect of the language in a claim. See MPEP 2103 I.C. and MPEP § 2111.04. The wherein clause directed to “the detectable signal comprises an elimination of the color signal produced by the RNA aptamer” represents an intended use of the system if it were to be used in a method. Furthermore, the wherein clause claims what can be reasonably considered as innate properties of the RNA-based masking construct comprising an RNA aptamer having a quadruplex with enzymatic activity that produces a color signal because the masking construct contains all the purported structural components needed to perform the wherein clause. For these reasons, it does not add further weight to the structure of the system.
Regarding instant claim 70, Nie, in view of Travascio, teaches the system of claim 2. Travascio further teaches wherein the enzymatic activity comprises peroxidase activity (Page 781, column 2, paragraph 2; Figure 2). Travascio does not directly teach wherein the peroxidase activity can oxidize a probe capable of generating a detectable signal in the presence of the enzymatic activity of the RNA aptamer's quadruplex. However, Travascio does teach that the peroxidase activity of the RNA aptamer quadruplex interacts with a substrate, causing oxidation which forms a color signal (Page 783, column 2, paragraph 1; Figure 3 showing an example with a DNA aptamer quadruplex). Therefore, it would be obvious to one of ordinary skill in the art that the RNA aptamer quadruplex could oxidize a probe capable of generating a detectable signal in the presence of the enzymatic activity of the RNA aptamer's quadruplex.
Regarding instant claim 71, Nie, in view of Travascio, teaches the system of claim 2. Travascio further teaches wherein the quadruplex is a quadruplex-hemin complex (Page 781, column 1, paragraph 3).
Regarding instant claim 72, Nie, in view of Travascio, teaches the system of claim 1. Nie, combined with Travascio, further teaches wherein the RNA-based masking construct does not include a fluorophore and a quencher of the fluorophore (see claim 1 rejection; Travascio, Page 780, columns 1 and 2, first paragraph in each column; Figure 1A).
Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Nie (CN107557455A; original text provided with translation) and Travascio (A ribozyme and a catalytic DNA with peroxidase activity: active sites versus cofactor-binding sites, Cell Chemical Biology, November 1999, 6, 779-787; previously cited) as applied to claims 1-4, 10, 12-13, 17, 19, 39, and 69-72, and further in view of East-Seletsky (RNA targeting by functionally orthogonal Type VI-A CRISPR-Cas enzymes, Molecular Cell, May 2017, 66, 373-383; cited on the IDS filed January 10th, 2024; previously cited).
Regarding instant claim 5, Nie, in view of Travascio, teaches the system claim 1.
Neither reference teaches the binding domains of claim 5.
East-Seletsky, in the same field of endeavor, teaches wherein the RNA-targeting effector protein optionally comprises one or more higher eukaryotes and prokaryotes nucleotide-binding (HEPN) domains (Page 375, column 1; Figure 2A), East-Seletsky does not directly teach that these HEPN domains comprise a RxxxxH motif sequence, wherein the RxxxxH motif comprises a R{N/H/K}X1X2X3H sequence, and wherein X1 is R, S, D, E, Q, N, G, or Y, or X2 is independently I, S, T, V, or L, or X3 is independently L, F, N, Y, V, I, S, D, E, or A. However, East-Seletsky inherently teaches these limitations based on their selected Cas13 HEPN domain comparison (Supplementary Methods, Figure S2). As evidenced by UniProt submission CS13A_LISSS (P0DPB8 · CS13A_LISSS [online]. UniProt, [originally provided November 2017] [retrieved on July 7th, 2025]. Retrieved from: https://www.uniprot.org/uniprotkb/P0DPB8/entry; previously cited), this submission discloses an amino acid sequence of Cas13a from Listeria seeligeri serovar 1/2b str. SLCC3954 (Supplementary Methods, Figure S2), wherein the amino acid sequence DDA - RDVL SY DRK LK NAV SK SLK ELS corresponds to amino acids 1038-1062 and the claimed [N]X1X2X3H sequence, wherein X1 is N, and X2 is I, and X3 is S corresponds to amino acids 1016-1021. Therefore, the claimed limitation of the [N]X1X2X3H sequence, wherein X1 is N, X2 is I, and X3 is S is inherently present in East-Seletsky.
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the RNA-targeting effector protein of Nie with the HEPN domains of East-Seletsky. Since both Nie and East-Seletsky are in the same field of endeavor, one of ordinary skill in the art would combine the two teachings with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to make this modification because these domains may play pivotal roles in pre-crRNA processing by stabilizing substrate binding, promoting proper substrate orientation, and/or catalyzing hydrolysis (East-Seletsky, Page 375, column 2, paragraph 1).
Claim 16 is rejected under 35 U.S.C. 103 as being unpatentable over Nie (CN107557455A; original text provided with translation) and Travascio (A ribozyme and a catalytic DNA with peroxidase activity: active sites versus cofactor-binding sites, Cell Chemical Biology, November 1999, 6, 779-787; previously cited) as applied to claims 1-4, 10, 12-13, 17, 19, 39, and 69-72, and further in view of Li (CN107462570A; previously cited).
Regarding instant claim 16, Nie, in view of Travascio, teaches the system of claim 1.
Neither reference teaches wherein the RNA aptamer can bind to ochratoxin A (OTA).
In a general teaching, Li discusses an aptamer that can bind to ochratoxin A (abstract). Li teaches that ochratoxins are a class of highly toxic metabolites produced by toxin-producing strains of Penicillium and Aspergillus. Li teaches that Ochratoxin A (OTA) is the most toxic, widely distributed and most harmful to the human body toxin (Page 2, paragraph [0004]). Li teaches OTA-aptamers for detecting ochratoxin A (see entire document). Based on this, it is of great practical significance to research and develop a new technology and method for detecting ochratoxin A with low detection cost, short detection time, small amount of reagents and high sensitivity (Page 2, paragraph [0004]). Li teaches that the purpose of the invention aims at the problem of the existing technology by providing a photonic crystal modified microsphere for detecting OTA based on the DNAzyme-aptamer chemiluminescence method, which uses three-dimensional photonic crystal microspheres as a carrier, takes aptamer technology as the reaction basis, and uses the G-quadruplex structure formed by hemin and DNA chain as a bioenzyme catalyzed luminol system for chemiluminescence, thereby constructing a method for detecting OTA (ochratoxin A) with high sensitivity and high throughput (Page 3, paragraph [0006]).
It would have been prima facie obvious to one of ordinary skill in the art to have been motivated to utilize an aptamer which can bind ochratoxin A as taught by Li in the nucleic acid detection system as taught by Nie, in view of Travascio, because Li explains the significance of ochratoxin A as a toxin produced by a fungal species similar to penicillium or Aspergillus that has strong toxicity for metabolites and can promote damage to the human body (Li, Page 2, paragraph [0004]). The artisan of ordinary skill would have been motivated to do this for the obvious benefit of detecting toxin that may be harmful to humans.
Claims 20, 25, and 27 are rejected under 35 U.S.C. 103 as being unpatentable over Nie (CN107557455A; original text provided with translation), Travascio (A ribozyme and a catalytic DNA with peroxidase activity: active sites versus cofactor-binding sites, Cell Chemical Biology, November 1999, 6, 779-787; previously cited), as applied to claims 1-4, 10, 12-13, 17, 19, 39, and 69-72, and further in view of Chen (CRISPR-Cas12a target binding unleashes single-stranded DNase activity, bioRxiv, November 2017, 1-29, https://doi.org/10.1101/226993).
Regarding instant claim 20, Nie, in view of Travascio, teaches the system of claim 1. Nie teaches wherein the one or more guide RNAs are designed to bind to one or more target molecules (Page 19, paragraph [0026]).
Neither reference teaches wherein the one or more guide RNAs are designed to bind to one or more target molecules that are diagnostic for a disease state, wherein optionally the disease state is an infection optionally caused by a virus or a bacterium.
Chen, in a reasonably pertinent field, teaches wherein a guide RNA is designed to bind to a target molecule diagnostic for a disease state (Page 6, paragraph 2; Figure 3C), wherein optionally the disease state is an infection optionally caused by a virus or a bacterium (Page 6, paragraph 2; Figure 3C).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the system of Nie, in view of Travascio with the guide RNA design of Chen. Since Chen teaches on CRISPR detection systems, which is reasonably pertinent to the CRISPR detection system of Nie, in view of Travascio, one of ordinary skill in the art would combine the two teachings with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to make this modification because it amount to simple substitution of one known element for another to obtain predictable results (see MPEP 2141(III)). While Chen teaches this design in relation to the Cas12a protein, which detects DNA targets, it would be obvious that the same principles of design could be used for detection of disease with Cas13a given the teachings of Nie related to guide RNA matching a fragment of a target RNA.
Regarding instant claim 25, Nie, in view of Travascio and Chen, teaches the system of claim 20. Nie further teaches wherein the infection is a viral infection optionally caused by a DNA virus (Page 6, paragraph 2).
Regarding instant claim 27, Gootenberg, in view of Travascio and Chen, teaches the system of claim 25. Chen further teaches wherein the DNA virus is Papillomaviridae (Page 6, paragraph 2).
Claims 28 and 29 are rejected under 35 U.S.C. 103 as being unpatentable over Nie (CN107557455A; original text provided with translation), Travascio (A ribozyme and a catalytic DNA with peroxidase activity: active sites versus cofactor-binding sites, Cell Chemical Biology, November 1999, 6, 779-787; previously cited), and Chen (CRISPR-Cas12a target binding unleashes single-stranded DNase activity, bioRxiv, November 2017, 1-29, https://doi.org/10.1101/226993) as applied to claim 20, and further in view of Channappanavar (Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology, Seminars in Immunopathology, May 2017, 39, 529-539).
Regarding instant claim 28, Nie, in view of Travascio and Chen, teaches the system of claim 20. Chen teaches wherein the infection is a viral infection (Page 6, paragraph 2).
None of the references teach wherein the infection is a viral infection caused by a double-stranded RNA virus, a positive sense RNA virus, a negative sense RNA virus, a retrovirus, or a combination thereof.
Channappanavar, in a reasonably pertinent field, teaches that an infection can be caused by a positive sense RNA virus (Page 529, column 2, paragraph 1).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the nucleic acid detection system diagnostic for a disease state caused by an infection as described in Gootenberg, in view of Travascio, with the positive sense RNA virus infection from Channappanavar. Since Channappanavar teaches that a positive sense RNA virus can cause an infection, which is reasonably pertinent to a nucleic acid detection system diagnostic for a disease state caused by an infection, one of ordinary skill in the art would combine the two teachings with a reasonable expectation of success.
Regarding instant claim 29, Nie, in view of Travascio, Chen, and Channappanavar, teaches the system of claim 28. Channappanavar further teaches that a viral infection can be caused by a positive sense RNA virus from the family Coronaviridae (Page 529, column 2, paragraph 1).
Claim 31 is rejected under 35 U.S.C. 103 as being unpatentable over Nie (CN107557455A; original text provided with translation), Travascio (A ribozyme and a catalytic DNA with peroxidase activity: active sites versus cofactor-binding sites, Cell Chemical Biology, November 1999, 6, 779-787; previously cited), and Chen (CRISPR-Cas12a target binding unleashes single-stranded DNase activity, bioRxiv, November 2017, 1-29, https://doi.org/10.1101/226993) as applied to claim 20, and further in view of Van Rie et al. (Reinfection and Mixed Infection Cause Changing Mycobacterium tuberculosis Drug-Resistance Patterns, American Journal of Respiratory and Critical Care Medicine, 2005, 172, 636-642; previously cited).
Regarding instant claim 31, Nie, in view of Travascio and Chen, teaches the system of claim 20.
None of the references teach wherein the infection is caused by a bacterium, nor that the bacterium is a particular species.
Van Rie, in a reasonably pertinent field, teaches that an infection can be caused by a Mycobacterium species (Introduction).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the nucleic acid detection system diagnostic for a disease state caused by an infection as described in Nie, in view of Travascio and Chen, with the Mycobacterium species infection from Van Rie. Since Van Rie teaches that a Mycobacterium species can cause an infection, which is reasonably pertinent to a nucleic acid detection system diagnostic for a disease state caused by an infection, one of ordinary skill in the art would combine the two teachings with a reasonable expectation of success.
Claim 33 is rejected under 35 U.S.C. 103 as being unpatentable over Nie (CN107557455A; original text provided with translation), Travascio (A ribozyme and a catalytic DNA with peroxidase activity: active sites versus cofactor-binding sites, Cell Chemical Biology, November 1999, 6, 779-787; previously cited), and Chen (CRISPR-Cas12a target binding unleashes single-stranded DNase activity, bioRxiv, November 2017, 1-29, https://doi.org/10.1101/226993) as applied to claim 20, and further in view of Gigliotti et al. (Pneumocystis, Cold Spring Harbor Perspectives in Medicine, December 2014, 12, 1-14; previously cited).
Regarding instant claim 33, Nie, in view of Travascio and Chen, teaches the system of claim 20.
None of the references teach wherein the infection is caused by a fungus, nor that the fungus is a particular genus.
Gigliotti, in a reasonably pertinent field, teaches that an infection can be caused by a fungus (Abstract). Gigliotti also teaches that an infection can be caused by a fungus from the genus Pneumocystis (Abstract).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the nucleic acid detection system diagnostic for a disease state caused by an infection as described in Nie, in view of Travascio and Chen, with the fungal infection from Gigliotti. Since Gigliotti teaches that a fungus can cause an infection, which is reasonably pertinent to a nucleic acid detection system diagnostic for a disease state caused by an infection, one of ordinary skill in the art would combine the two teachings with a reasonable expectation of success.
Claim 35 is rejected under 35 U.S.C. 103 as being unpatentable over Nie (CN107557455A; original text provided with translation), Travascio (A ribozyme and a catalytic DNA with peroxidase activity: active sites versus cofactor-binding sites, Cell Chemical Biology, November 1999, 6, 779-787; previously cited), and Chen (CRISPR-Cas12a target binding unleashes single-stranded DNase activity, bioRxiv, November 2017, 1-29, https://doi.org/10.1101/226993) as applied to claim 20, and further in view of Trabelsi et al. (Pathogenic free-living amoebae: Epidemiology and clinical review, Pathologie Biologie, December 2012, 60, 399-405; previously cited).
Regarding instant claim 35, Nie, in view of Travascio and Chen, teaches the system of claim 20.
None of the references teach wherein the infection is caused by a protozoan, nor that the protazoan is a particular genus.
Trabelsi, in a reasonably pertinent field, teaches that an infection can be caused by a protozoa from the genus Amoebozoa (Introduction).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the nucleic acid detection system diagnostic for a disease state caused by an infection as described in Nie, in view of Travascio and Chen, with the Amoebozoa protozoal infection from Trabelsi. Since Trabelsi teaches that a Amoebozoa protozoan can cause an infection, which is reasonably pertinent to a nucleic acid detection system diagnostic for a disease state caused by an infection, one of ordinary skill in the art would combine the two teachings with a reasonable expectation of success.
Claim 37 is rejected under 35 U.S.C. 103 as being unpatentable over Nie (CN107557455A; original text provided with translation), Travascio (A ribozyme and a catalytic DNA with peroxidase activity: active sites versus cofactor-binding sites, Cell Chemical Biology, November 1999, 6, 779-787; previously cited), and Chen (CRISPR-Cas12a target binding unleashes single-stranded DNase activity, bioRxiv, November 2017, 1-29, https://doi.org/10.1101/226993) as applied to claim 20, and further in view of Ashley et al. (The duration of Plasmodium falciparum infections, Malaria Journal, December 2014, 13, 1-11; previously cited).
Regarding instant claim 37, Nie, in view of Travascio and Chen, teaches the system of claim 20.
Neither reference teaches wherein the infection is caused by a parasite, nor that it is a particular species.
Ashley, in a reasonably pertinent field, teaches that an infection can be caused by the parasite Plasmodium falciparum (Abstract).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the nucleic acid detection system diagnostic for a disease state caused by an infection as described in Nie, in view of Travascio and Chen, with the Plasmodium falciparum infection from Ashley. Since Ashley teaches that Plasmodium falciparum can cause an infection, which is reasonably pertinent to a nucleic acid detection system diagnostic for a disease state caused by an infection, one of ordinary skill in the art would combine the two teachings with a reasonable expectation of success.
Claims 40 and 43 are rejected under 35 U.S.C. 103 as being unpatentable over Nie (CN107557455A; original text provided with translation) and Travascio (A ribozyme and a catalytic DNA with peroxidase activity: active sites versus cofactor-binding sites, Cell Chemical Biology, November 1999, 6, 779-787; previously cited), as applied to claims 1-4, 10, 12-13, 17, 19, 39, and 69-72, and further in view of Cann (US 20160017396 A1; previously cited).
Regarding instant claim 40, Nie, in view of Travascio, teaches the system of claim 1.
Neither reference teaches that the system further comprises an enrichment CRISPR system designed to bind the target molecule prior to detection by the detection CRISPR system, wherein the enrichment CRISPR system optionally comprises a catalytically inactive CRISPR effector protein, optionally a catalytically inactive C2c2.
Cann, in a reasonably pertinent field, teaches an enrichment CRISPR system designed to bind the target molecule prior to further applications of the target molecule (Page 12, paragraph [0129]).
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the system of Nie with the enrichment CRISPR system from Cann. Since Cann teaches the enrichment CRISPR system can be used to bind target nucleic acids, which is reasonably pertinent to the CRISPR system of Nie, one of ordinary skill in the art would combine the two teachings with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to make this modification because CRISPR-Cas mediated nucleic acid binding is enzyme-driven, and thus it can offer faster kinetics and easier workflows for enrichment with lower temperature and/or isothermal reaction conditions (Page 12, paragraph [0129]).
It is noted that the subject matter of a properly construed claim is defined by the terms that limit its scope. It is this subject matter that must be examined. As a general matter, the grammar and intended meaning of terms used in a claim will dictate whether the language limits the claim scope. Language that suggests or makes optional but does not require steps to be performed or does not limit a claim to a particular structure does not limit the scope of a claim or claim limitation. “Optionally” clauses are examples of language that may raise a question as to the limiting effect of the language in a claim. See MPEP 2103 I.C. and MPEP § 2111.04. The optionally clauses directed to a catalytically inactive CRISPR effector protein and a catalytically inactive C2c2 are not required given their optionality.
Regarding instant claim 43, Nie, in view of Travascio and Cann, teaches the system of claim 40. Cann further teaches wherein the enrichment CRISPR system comprising the catalytically inactive CRISPR effector protein further comprises a tag, wherein the tag is used to pull down the enrichment CRISPR effector system (Page 12, paragraph [0142]).
Response to Arguments
The declaration under 37 CFR 1.130(a) filed on March 16th, 2026 is sufficient to overcome the rejection of claims 1-5, 10, 12-13, 16-17, 19-20, 25, 27-29, 31, 33, 35, 37, 39-40, 43, 69-72, and 73-75 based on Gootenberg or combinations with Gootenberg under 35 U.S.C. 103. The declaration provides evidence of reliance on the 35 U.S.C. 102(b)(1)(A) exception provision (Grace Period Disclosure by Inventor or Obtained from Inventor). Therefore, the rejections under Gootenberg and combinations with Gootenberg have been withdrawn. However, upon further consideration, new grounds of rejection is made in view of Nie and combinations with Nie.
Double Patenting – Maintained
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 1-5, 10, 12-13, 16-17, 19-20, 25, 27-29, 31, 33, 35, 37, 39-40, 43, and 69-72 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of U.S. Patent No. 10266886B2, in view of Nie (CN107557455A; original text provided with translation), Travascio (A ribozyme and a catalytic DNA with peroxidase activity: active sites versus cofactor-binding sites, Cell Chemical Biology, November 1999, 6, 779-787; previously cited), East-Seletsky (RNA targeting by functionally orthogonal Type VI-A CRISPR-Cas enzymes, Molecular Cell, May 2017, 66, 373-383; cited on the IDS filed January 10th, 2024; previously cited), Li (CN107462570A; previously cited), Chen (CRISPR-Cas12a target binding unleashes single-stranded DNase activity, bioRxiv, November 2017, 1-29, https://doi.org/10.1101/226993), Channappanavar (Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology, Seminars in Immunopathology, May 2017, 39, 529-539), Van Rie et al. (Reinfection and Mixed Infection Cause Changing Mycobacterium tuberculosis Drug-Resistance Patterns, American Journal of Respiratory and Critical Care Medicine, 2005, 172, 636-642; previously cited), Gigliotti et al. (Pneumocystis, Cold Spring Harbor Perspectives in Medicine, December 2014, 12, 1-14; previously cited), Trabelsi et al. (Pathogenic free-living amoebae: Epidemiology and clinical review, Pathologie Biologie, December 2012, 60, 399-405; previously cited), Ashley et al. (The duration of Plasmodium falciparum infections, Malaria Journal, December 2014, 13, 1-11; previously cited), and Cann (US 20160017396 A1; previously cited). Although the claims at issue are not identical, they are not patentably distinct from each other because both the ‘886 patent and the instant application claim a nucleic acid detection system comprising a Type VI CRISPR-Cas RNA targeting effector protein that exhibits collateral activity, including similar specific Type VI CRISPR-Cas RNA targeting effector proteins and particular domains; guide RNAs; an RNA-based masking construct; and amplification reagents, including similar amplification methods to use them in.
The ‘886 patent claims do not require a masking construct that is an RNA aptamer-quadruplex. However, Nie, in view of Travascio, teaches the claimed limitations directed to a masking construct that is an RNA aptamer-quadruplex (see claim 1 rejection), obviating these variations. Nie, in view of the provided art in the 103 rejections above, also teaches Type VI CRISPR-Cas RNA targeting effector protein originating organisms; guide RNAs, including specific design components; detection of disease states, including infections; and an enrichment system, obviating these variations to the system of the ‘886 patent. Any additional limitations of the claims of U.S. Patent No. 10266886B2 are encompassed by the open claim language “comprising” found in the instant claims.
Claims 1-5, 10, 12-13, 16-17, 19-20, 25, 27-29, 31, 33, 35, 37, 39-40, 43, and 69-72 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 10266887B2, in view of Nie (CN107557455A; original text provided with translation), Travascio (A ribozyme and a catalytic DNA with peroxidase activity: active sites versus cofactor-binding sites, Cell Chemical Biology, November 1999, 6, 779-787; previously cited), East-Seletsky (RNA targeting by functionally orthogonal Type VI-A CRISPR-Cas enzymes, Molecular Cell, May 2017, 66, 373-383; cited on the IDS filed January 10th, 2024; previously cited), Li (CN107462570A; previously cited), Chen (CRISPR-Cas12a target binding unleashes single-stranded DNase activity, bioRxiv, November 2017, 1-29, https://doi.org/10.1101/226993), Channappanavar (Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology, Seminars in Immunopathology, May 2017, 39, 529-539), Van Rie et al. (Reinfection and Mixed Infection Cause Changing Mycobacterium tuberculosis Drug-Resistance Patterns, American Journal of Respiratory and Critical Care Medicine, 2005, 172, 636-642; previously cited), Gigliotti et al. (Pneumocystis, Cold Spring Harbor Perspectives in Medicine, December 2014, 12, 1-14; previously cited), Trabelsi et al. (Pathogenic free-living amoebae: Epidemiology and clinical review, Pathologie Biologie, December 2012, 60, 399-405; previously cited), Ashley et al. (The duration of Plasmodium falciparum infections, Malaria Journal, December 2014, 13, 1-11; previously cited), and Cann (US 20160017396 A1; previously cited). Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘887 patent claims a method of detecting nucleic acids using a Type VI CRISPR-Cas RNA targeting effector protein that exhibits collateral activity, including similar specific Type VI CRISPR-Cas RNA targeting effector proteins and particular domains; guide RNAs; an RNA-based masking construct; aptamers; and amplification reagents, including similar amplification methods to use them in.
While the ‘887 patent does not claim the detection system itself, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use the instantly claimed system in the method of ‘887 to detect nucleic acids.
The ‘887 patent claims do not require a masking construct that is an RNA aptamer-quadruplex. However, Nie, in view of Travascio, teaches the claimed limitations directed to a masking construct that is an RNA aptamer-quadruplex (see claim 1 rejection), obviating this variation. Nie, in view of the provided art in the 103 rejections above, also teaches Type VI CRISPR-Cas RNA targeting effector protein originating organisms; guide RNAs, including specific design components; detection of disease states, including infections; and an enrichment system, obviating these variations to the method of the ‘887 patent (see 103 rejections). Any additional limitations of the claims of U.S. Patent No. 10266887B2 are encompassed by the open claim language “comprising” found in the instant claims.
Claims 1-5, 10, 12-13, 16-17, 19-20, 25, 27-29, 31, 33, 35, 37, 39-40, 43, and 69-72 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 12-22 and 25 of U.S. Patent No. 11021740B2, in view of Nie (CN107557455A; original text provided with translation), Travascio (A ribozyme and a catalytic DNA with peroxidase activity: active sites versus cofactor-binding sites, Cell Chemical Biology, November 1999, 6, 779-787; previously cited), East-Seletsky (RNA targeting by functionally orthogonal Type VI-A CRISPR-Cas enzymes, Molecular Cell, May 2017, 66, 373-383; cited on the IDS filed January 10th, 2024; previously cited), Li (CN107462570A; previously cited), Chen (CRISPR-Cas12a target binding unleashes single-stranded DNase activity, bioRxiv, November 2017, 1-29, https://doi.org/10.1101/226993), Channappanavar (Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology, Seminars in Immunopathology, May 2017, 39, 529-539), Van Rie et al. (Reinfection and Mixed Infection Cause Changing Mycobacterium tuberculosis Drug-Resistance Patterns, American Journal of Respiratory and Critical Care Medicine, 2005, 172, 636-642; previously cited), Gigliotti et al. (Pneumocystis, Cold Spring Harbor Perspectives in Medicine, December 2014, 12, 1-14; previously cited), Trabelsi et al. (Pathogenic free-living amoebae: Epidemiology and clinical review, Pathologie Biologie, December 2012, 60, 399-405; previously cited), Ashley et al. (The duration of Plasmodium falciparum infections, Malaria Journal, December 2014, 13, 1-11; previously cited), and Cann (US 20160017396 A1; previously cited). Although the claims at issue are not identical, they are not patentably distinct from each other because both the ‘740 patent claims a device for detecting nucleic acids comprising a Type VI CRISPR-Cas RNA targeting effector protein that exhibits collateral activity, including similar specific Type VI CRISPR-Cas RNA targeting effector proteins, originating organisms, and particular domains; guide RNAs, including similar specific design components; an RNA-based masking construct that can be a quadruplex; aptamers; amplification reagents, including similar amplification methods to use them in.
While the ‘740 patent does not claim the detection system itself, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use the automated detection device of the ‘740 patent in the system of the instant application. See In re Venner, 262 F.2d 91, 120 USPQ 193 (CCPA (1958), where the court held that broadly providing an automatic or mechanical means to replace a manual activity which accomplished the same result is not sufficient to distinguish over the prior art.
The ‘740 patent claims do not require detection of disease states, including cancer and infections; and an enrichment system. However, Nie, in view of the provided art in the 103 rejections above, teaches detection of disease states, including infections; and an enrichment system, obviating these variations to the device of the ‘740 patent (see 103 rejections). Any additional limitations of the claims of U.S. Patent No. 11021740B2 are encompassed by the open claim language “comprising” found in the instant claims.
Claims 1-5, 10, 12-13, 16-17, 19-20, 25, 27-29, 31, 33, 35, 37, 39-40, 43, and 69-72 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2 and 11-25 of U.S. Patent No. 11104937B2, in view of Nie (CN107557455A; original text provided with translation), Travascio (A ribozyme and a catalytic DNA with peroxidase activity: active sites versus cofactor-binding sites, Cell Chemical Biology, November 1999, 6, 779-787; previously cited), East-Seletsky (RNA targeting by functionally orthogonal Type VI-A CRISPR-Cas enzymes, Molecular Cell, May 2017, 66, 373-383; cited on the IDS filed January 10th, 2024; previously cited), Li (CN107462570A; previously cited), Chen (CRISPR-Cas12a target binding unleashes single-stranded DNase activity, bioRxiv, November 2017, 1-29, https://doi.org/10.1101/226993), Channappanavar (Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology, Seminars in Immunopathology, May 2017, 39, 529-539), Van Rie et al. (Reinfection and Mixed Infection Cause Changing Mycobacterium tuberculosis Drug-Resistance Patterns, American Journal of Respiratory and Critical Care Medicine, 2005, 172, 636-642; previously cited), Gigliotti et al. (Pneumocystis, Cold Spring Harbor Perspectives in Medicine, December 2014, 12, 1-14; previously cited), Trabelsi et al. (Pathogenic free-living amoebae: Epidemiology and clinical review, Pathologie Biologie, December 2012, 60, 399-405; previously cited), Ashley et al. (The duration of Plasmodium falciparum infections, Malaria Journal, December 2014, 13, 1-11; previously cited), and Cann (US 20160017396 A1; previously cited). Although the claims at issue are not identical, they are not patentably distinct from each other because both the ‘937 patent and the instant application claim a nucleic acid detection system comprising a Type VI CRISPR-Cas RNA targeting effector protein that exhibits collateral activity, including similar specific Type VI CRISPR-Cas RNA targeting effector proteins; guide RNAs; an RNA-based masking construct; amplification reagents; and detection of disease states, including infections. The ‘937 patent expands the system to be included in a method; however, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use the instantly claimed system in the method of ‘937 to detect nucleic acids because the ‘937 patent claims use of a system in the method.
The ‘937 patent claims do not require a masking construct that is an RNA aptamer-quadruplex. However, Nie, in view of Travascio, teaches the claimed limitations directed to a masking construct that is an RNA aptamer-quadruplex (see claim 1 rejection), obviating this variation. Nie, in view of the provided art in the 103 rejections above, also teaches Type VI CRISPR-Cas RNA targeting effector protein originating organisms and particular domains; guide RNAs, including specific design components; detection of disease states, including cancer and infections; and an enrichment system, obviating these variations to the system and method of the ‘937 patent (see 103 rejections). Any additional limitations of the claims of U.S. Patent No. 11104937B2 are encompassed by the open claim language “comprising” found in the instant claims.
Claims 1-5, 10, 12-13, 16-17, 19-20, 25, 27-29, 31, 33, 35, 37, 39-40, 43, and 69-72 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-35 of U.S. Patent No. 11174515B2. Although the claims at issue are not identical, they are not patentably distinct from each other because both the ‘515 patent and the instant application claim a nucleic acid detection system comprising a Type VI CRISPR-Cas RNA targeting effector protein that exhibits collateral activity, including similar specific Type VI CRISPR-Cas RNA targeting effector proteins, originating organisms, and particular domains; guide RNAs, including similar specific design components; an RNA-based masking construct that can be a quadruplex; aptamers; amplification reagents, including similar amplification methods to use them in; detection of disease states, including cancer and infections; and an enrichment system. The ‘515 patent claims a list of different detectable mutations that guide sequences correspond to, which are encompassed by the guide RNAs designed to base pair to a generic complementary target nucleotide sequence of a target molecule in the instant application. Any additional limitations of the claims of U.S. Patent No. 11174515B2 are encompassed by the open claim language “comprising” found in the instant claims.
Claims 1-5, 10, 12-13, 16-17, 19-20, 25, 27-29, 31, 33, 35, 37, 39-40, 43, and 69-72 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 of U.S. Patent No. 11618928B2. Although the claims at issue are not identical, they are not patentably distinct from each other because both the ‘928 patent and the instant application claim nucleic acid detection systems comprising Cas protein(s), guide RNAs and detection (i.e., masking) construct. The ‘928 patent claims are encompassed by the claims of the instant application, and thus the claims of the ‘928 patent and the instant application are not patentably distinct. Any additional limitations of the claims of U.S. Patent No. 11618928B2 are encompassed by the open claim language “comprising” found in the instant claims.
Claims 1-5, 10, 12-13, 16-17, 19-20, 25, 27-29, 31, 33, 35, 37, 39-40, 43, and 69-72 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-4, 9-20, and 23 of U.S. Patent No. 11633732B2, in view of Nie (CN107557455A; original text provided with translation), Travascio (A ribozyme and a catalytic DNA with peroxidase activity: active sites versus cofactor-binding sites, Cell Chemical Biology, November 1999, 6, 779-787; previously cited), East-Seletsky (RNA targeting by functionally orthogonal Type VI-A CRISPR-Cas enzymes, Molecular Cell, May 2017, 66, 373-383; cited on the IDS filed January 10th, 2024; previously cited), Li (CN107462570A; previously cited), Chen (CRISPR-Cas12a target binding unleashes single-stranded DNase activity, bioRxiv, November 2017, 1-29, https://doi.org/10.1101/226993), Channappanavar (Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology, Seminars in Immunopathology, May 2017, 39, 529-539), Van Rie et al. (Reinfection and Mixed Infection Cause Changing Mycobacterium tuberculosis Drug-Resistance Patterns, American Journal of Respiratory and Critical Care Medicine, 2005, 172, 636-642; previously cited), Gigliotti et al. (Pneumocystis, Cold Spring Harbor Perspectives in Medicine, December 2014, 12, 1-14; previously cited), Trabelsi et al. (Pathogenic free-living amoebae: Epidemiology and clinical review, Pathologie Biologie, December 2012, 60, 399-405; previously cited), Ashley et al. (The duration of Plasmodium falciparum infections, Malaria Journal, December 2014, 13, 1-11; previously cited), and Cann (US 20160017396 A1; previously cited). Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘732 patent claims a device for detecting nucleic acids comprising a system of a Type VI CRISPR-Cas RNA targeting effector protein that exhibits collateral activity, including similar specific Type VI CRISPR-Cas RNA targeting effector proteins and originating organisms; guide RNAs; detection of disease states, including cancer and infections; and amplification reagents, including similar amplification methods to use them in.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use the automated detection device of the ‘732 patent in the system of the instant application. See In re Venner, 262 F.2d 91, 120 USPQ 193 (CCPA (1958), where the court held that broadly providing an automatic or mechanical means to replace a manual activity which accomplished the same result is not sufficient to distinguish over the prior art.
The ‘732 patent claims do not require a masking construct that is an RNA-based masking construct that can be a quadruplex. However, Nie, in view of Travascio, teaches the claimed limitations directed to a masking construct that is an RNA aptamer-quadruplex (see claim 1 rejection), obviating these variations. Nie, in view of the provided art in the 103 rejections above, also teaches Type VI CRISPR-Cas RNA targeting effector proteins domains; guide RNAs, including similar specific design components; aptamers; and an enrichment system. Any additional limitations of the claims of U.S. Patent No. 11633732B2 are encompassed by the open claim language “comprising” found in the instant claims.
Claims 1-5, 10, 12-13, 16-17, 19-20, 25, 27-29, 31, 33, 35, 37, 39-40, 43, and 69-72 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 19007301 (reference application), in view of Nie (CN107557455A; original text provided with translation), Travascio (A ribozyme and a catalytic DNA with peroxidase activity: active sites versus cofactor-binding sites, Cell Chemical Biology, November 1999, 6, 779-787; previously cited), East-Seletsky (RNA targeting by functionally orthogonal Type VI-A CRISPR-Cas enzymes, Molecular Cell, May 2017, 66, 373-383; cited on the IDS filed January 10th, 2024; previously cited), Li (CN107462570A; previously cited), Chen (CRISPR-Cas12a target binding unleashes single-stranded DNase activity, bioRxiv, November 2017, 1-29, https://doi.org/10.1101/226993), Channappanavar (Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology, Seminars in Immunopathology, May 2017, 39, 529-539), Van Rie et al. (Reinfection and Mixed Infection Cause Changing Mycobacterium tuberculosis Drug-Resistance Patterns, American Journal of Respiratory and Critical Care Medicine, 2005, 172, 636-642; previously cited), Gigliotti et al. (Pneumocystis, Cold Spring Harbor Perspectives in Medicine, December 2014, 12, 1-14; previously cited), Trabelsi et al. (Pathogenic free-living amoebae: Epidemiology and clinical review, Pathologie Biologie, December 2012, 60, 399-405; previously cited), Ashley et al. (The duration of Plasmodium falciparum infections, Malaria Journal, December 2014, 13, 1-11; previously cited), and Cann (US 20160017396 A1; previously cited). Although the claims at issue are not identical, they are not patentably distinct from each other because both the ‘301 reference application and the instant application claim a nucleic acid detection system comprising a Type VI CRISPR-Cas RNA targeting effector protein that exhibits collateral activity, guide RNAs, an RNA-based masking construct, and amplification reagents.
The ‘301 application claims do not require a nucleic acid detection system comprising a Type VI CRISPR-Cas RNA targeting effector protein that exhibits collateral activity, including similar specific Type VI CRISPR-Cas RNA targeting effector proteins, originating organisms, and particular domains; guide RNAs, including similar specific design components; an RNA-based masking construct that can be a quadruplex; aptamers; amplification reagents, including similar amplification methods to use them in; detection of disease states, including cancer and infections; and an enrichment system. However, Nie, in view of the provided art in the 103 rejections above, teaches the claimed limitations as discussed in the above 103 rejections, obviating these variations to the of the ‘301 application. Any additional limitations of the claims of Application No. 19007301 are encompassed by the open claim language “comprising” found in the instant claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-5, 10, 12-13, 16-17, 19-20, 25, 27-29, 31, 33, 35, 37, 39-40, 43, and 69-72 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-5, 8, 11 and 12 of copending Application No. 17495219.
Although the claims at issue are not identical, they are not patentably distinct from each other because both the ‘219 reference application and the instant application claim a nucleic acid detection system comprising a Type VI CRISPR-Cas RNA targeting effector protein that exhibits collateral activity, including similar specific Type VI CRISPR-Cas RNA targeting effector proteins, originating organisms, and particular domains; guide RNAs, including similar specific design components; an RNA-based masking construct that can be a quadruplex; aptamers; amplification reagents, including similar amplification methods to use them in; detection of disease states; and an enrichment system. The ‘219 reference application claims a list of different detectable mutations that guide sequences correspond to, which are encompassed by the guide RNAs designed to base pair to a generic complementary target nucleotide sequence of a target molecule in the instant application. Any additional limitations of the claims of Application No. 17495219 are encompassed by the open claim language “comprising” found in the instant claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-5, 10, 12-13, 16-17, 19-20, 25, 27-29, 31, 33, 35, 37, 39-40, 43, and 69-72 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 9, 13-15, and 18-21 of copending Application No. 18772681 in view of Nie (CN107557455A; original text provided with translation), Travascio (A ribozyme and a catalytic DNA with peroxidase activity: active sites versus cofactor-binding sites, Cell Chemical Biology, November 1999, 6, 779-787; previously cited), East-Seletsky (RNA targeting by functionally orthogonal Type VI-A CRISPR-Cas enzymes, Molecular Cell, May 2017, 66, 373-383; cited on the IDS filed January 10th, 2024; previously cited), Li (CN107462570A; previously cited), Chen (CRISPR-Cas12a target binding unleashes single-stranded DNase activity, bioRxiv, November 2017, 1-29, https://doi.org/10.1101/226993), Channappanavar (Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology, Seminars in Immunopathology, May 2017, 39, 529-539), Van Rie et al. (Reinfection and Mixed Infection Cause Changing Mycobacterium tuberculosis Drug-Resistance Patterns, American Journal of Respiratory and Critical Care Medicine, 2005, 172, 636-642; previously cited), Gigliotti et al. (Pneumocystis, Cold Spring Harbor Perspectives in Medicine, December 2014, 12, 1-14; previously cited), Trabelsi et al. (Pathogenic free-living amoebae: Epidemiology and clinical review, Pathologie Biologie, December 2012, 60, 399-405; previously cited), Ashley et al. (The duration of Plasmodium falciparum infections, Malaria Journal, December 2014, 13, 1-11; previously cited), and Cann (US 20160017396 A1; previously cited). Although the claims at issue are not identical, they are not patentably distinct from each other because both the ‘681 reference application and the instant application claim a nucleic acid detection system comprising a Type VI CRISPR-Cas RNA targeting effector protein that exhibits collateral activity, including similar specific Type VI CRISPR-Cas RNA targeting effector proteins and originating organisms; and guide RNAs, including similar specific design components.
The ‘681 application claims do not require a masking construct that is an RNA-based masking construct that can be a quadruplex. However, Nie, in view of Travascio, teaches the claimed limitations directed to a masking construct that is an RNA aptamer-quadruplex, as discussed in the above 103 rejections (see claim 1 rejection), obviating this variation. Nie, in view of the provided art in the 103 rejections above, also teaches Type VI CRISPR-Cas RNA targeting effector proteins domains; aptamers; amplification reagents, including amplification methods to use them in; detection of disease states; and an enrichment system, obviating these variations to the of the ‘681 application. Any additional limitations of the claims of Application No. 18772681 are encompassed by the open claim language “comprising” found in the instant claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-5, 10, 12-13, 16-17, 19-20, 25, 27-29, 31, 33, 35, 37, 39-40, 43, and 69-72 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 18-19, 32, 36-37, and 45 of copending Application No. 17640016 in view of Nie (CN107557455A; original text provided with translation), Travascio (A ribozyme and a catalytic DNA with peroxidase activity: active sites versus cofactor-binding sites, Cell Chemical Biology, November 1999, 6, 779-787; previously cited), East-Seletsky (RNA targeting by functionally orthogonal Type VI-A CRISPR-Cas enzymes, Molecular Cell, May 2017, 66, 373-383; cited on the IDS filed January 10th, 2024; previously cited), Li (CN107462570A; previously cited), Chen (CRISPR-Cas12a target binding unleashes single-stranded DNase activity, bioRxiv, November 2017, 1-29, https://doi.org/10.1101/226993), Channappanavar (Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology, Seminars in Immunopathology, May 2017, 39, 529-539), Van Rie et al. (Reinfection and Mixed Infection Cause Changing Mycobacterium tuberculosis Drug-Resistance Patterns, American Journal of Respiratory and Critical Care Medicine, 2005, 172, 636-642; previously cited), Gigliotti et al. (Pneumocystis, Cold Spring Harbor Perspectives in Medicine, December 2014, 12, 1-14; previously cited), Trabelsi et al. (Pathogenic free-living amoebae: Epidemiology and clinical review, Pathologie Biologie, December 2012, 60, 399-405; previously cited), Ashley et al. (The duration of Plasmodium falciparum infections, Malaria Journal, December 2014, 13, 1-11; previously cited), and Cann (US 20160017396 A1; previously cited). Although the claims at issue are not identical, they are not patentably distinct from each other because both the ‘016 reference application and the instant application claim a nucleic acid detection system comprising a Type VI CRISPR-Cas RNA targeting effector protein that exhibits collateral activity, including similar specific Type VI CRISPR-Cas RNA targeting effector proteins; guide RNAs; an RNA-based masking construct that can be a quadruplex; aptamers; amplification reagents, including similar amplification methods to use them in; and detection of disease states, including cancer. The ‘016 reference application claims detection of one or more cancers via optimized guide molecules designed to bind to cancer fusion genes, which are encompassed by the generic complementary target nucleotide sequence of a target molecule in the instant application.
The ‘016 application claims do not require particular Type VI CRISPR-Cas RNA targeting effector protein originating organisms and particular domains; guide RNAs, including similar specific design components; detection of disease states, including infections; and an enrichment system. However, Nie, in view of the provided art in the 103 rejections above, teaches these claimed limitations as discussed in the above 103 rejections, obviating these variations to the of the ‘016 application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
The declaration under 37 CFR 1.130(a) filed on March 16th, 2026 is sufficient to overcome the rejection of claims 1-5, 10, 12-13, 16-17, 19-20, 25, 27-29, 31, 33, 35, 37, 39-40, 43, 69-72, and 73-75 based on Gootenberg or combinations with Gootenberg under nonstatutory double patenting. The declaration provides evidence of reliance on the 35 U.S.C. 102(b)(1)(A) exception provision (Grace Period Disclosure by Inventor or Obtained from Inventor). Therefore, the rejections under Gootenberg and combinations with Gootenberg have been withdrawn. However, upon further consideration, new grounds of rejection is made in view of Nie and combinations with Nie.
Claim Objections
Claim 76 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
Claims 1-5, 10, 12-13, 16-17, 19-20, 25, 27-29, 31, 33, 35, 37, 39-40, 43, and 69-72 are rejected. Claim 76 is objected to for depending from a rejected base claim.
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/ALLISON E SCHLOOP/Examiner, Art Unit 1683
/Robert T. Crow/Primary Examiner, Art Unit 1683
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