DETAILED CORRESPONDENCE
Status of the Application
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 1-19, 62-69, 71, and 74-87 are pending in this application.
Applicant’s amendment to the claims filed 05/21/2025 is acknowledged. This listing of the claims replaces all prior versions and listings of the claims.
Applicant’s amendment to the specification filed 05/21/2025 is acknowledged.
Applicant’s amendment to the drawings filed 05/21/2025 is acknowledged.
Applicant’s remarks filed on 05/21/2025 in response to the non-final rejection mailed on 02/24/2025, and remarks filed on 09/05/2025 in response to the Notice for Non-Compliant Amendment mailed on 09/03/2025 are acknowledged and have been fully considered.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Election
The elected subject matter is
Group I, corresponding to claims 1-11, 71 and 78-84, drawn to a system comprising the combination of a Class 2 CRISPR-Cas endonuclease and a gRNA, a composition comprising the system, a kit comprising the system, a composition comprising the endonuclease, a polynucleotide encoding the endonuclease, a vector comprising the polynucleotide and a host cell comprising the vector, and
the species of SEQ ID NO: 1,
elected without traverse in the reply filed 10/21/2024.
The election without traverse of
the species of SEQ ID NOs: 116, 62 and 94 from Tables 7, 1, and 4, respectively
in the reply filed 09/05/2025 is acknowledged.
The species of SEQ ID NO: 62 from Table 1 is considered to correspond to the previously elected species of SEQ ID NO: 1, as both species correspond to a Class 2 Type V Cas endonuclease.
New claims 81-87 are drawn to a system comprising a Class 2 CRISPR-Cas endonuclease or a nucleic acid encoding the endonuclease, a gRNA or nucleic acid encoding the gRNA, and a composition comprising the engineered system of claim 82, and therefore are considered part of the elected invention of Group I.
Claims 12-19, 62-69 and 74-77 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 10/21/2024.
As the elected species SEQ ID NOs: 1 and 62 read on the system comprising a Type V CRISPR-Cas endonuclease, claims 2-3, 5, 7-9, and 11 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species. Election was made without traverse in the reply filed on 10/21/2024.
The elected species of SEQ ID NO: 62 is free of the prior art of record and in accordance with MPEP 803.02.III.A, the search and examination has been extended to the species of SEQ ID NO: 75.
Claims 1, 4, 6, 10, 71 and 78-87 are being examined on the merits only to the extent they read on the elected subject matter.
Information Disclosure Statement
The Information Disclosure Statements (IDSs) submitted on 08/01/2025 and 09/26/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the IDSs have been considered by the examiner.
Objections to Specification
The objections to the specification are withdrawn in view of the amendments to address the use of trademarks.
Objection to Drawings
The drawings submitted 05/21/2025 are objected to because Figures 8, 16, 18, 51 include sequences that are duplicated from the Sequence Listing XML. Pursuant to 37 CFR 1.83(a), sequences that are included in the "Sequence Listing XML" should not be duplicated in the drawings (see MPEP 2412.06).
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.
Response to Remarks: beginning on p. 15 of Applicant’s response to drawing objections; Applicant in summary contends the sequences shown in the drawings describe a significant characteristic of the invention that cannot be conveyed in a sequence listing according to MPEP 2412.06, such as the predicted structural features of proteins and functional domains.
Applicant’s remarks are considered and found not convincing, as there are sequences shown in figures 8, 16, 18 and 51 that do not display any structural features or proteins and functional domains, and merely recite the sequences from the sequence listing.
Claim Objections
The objection to claim 1 is withdrawn in view of the amendment to recite (a), (b), (i), (ii), and (iii) to distinguish the components of the claimed system.
Claim 82 is objected to for the phrase “wherein the Class 2 CRISPR-Cas endonuclease comprises … 90% sequence identity thereto”. In the interest of improving claim form, Applicant should consider an amendment to recite “wherein the Class 2 CRISPR-Cas endonuclease comprises … a sequence comprising 90% identity thereto”.
Claim Rejections - 35 USC § 112(b)
The rejection of claims 1, 4, 6, 10, 71 and 78-80 under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor as the invention are withdrawn in view of the amendment to claim 1 to refer to sequence identifiers.
Claim Rejections - 35 USC § 112(a)
Claim interpretation: The claims are drawn (in relevant part) to an engineered system comprising a Class 2 CRISPR-Cas endonuclease or nucleic acid encoding the endonuclease and a gRNA or nucleic acid encoding the gRNA, wherein the gRNA and endonuclease do not naturally occur together, wherein the gRNA is capable of hybridizing to a target sequence in a DNA or RNA sequence, and the gRNA is capable of forming a complex with the endonuclease. The endonuclease is further limited to containing a RuvC sequence or HEPN sequence of at least 90% identity to the sequences disclosed in the claim. As the Class 2 CRISPR-Cas endonuclease is structurally defined by having > 90% sequence identity with domains as small as 12 amino acids, and is without structural limitation to the full length polypeptide, the remaining amino acid sequence of the Class 2 CRISPR-Cas endonuclease is considered unlimited. As such, the genus of recited Class 2 CRISPR-Cas endonucleases encompasses species that are considered to be widely variant with respect to sequence.
Claims 1, 4, 6, 71 and 78-81 are rejected under 35 U.S.C. 112(a) as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor at the time the application was filed, had possession of the claimed invention.
The instant rejection is maintained from the previous office action, and has been modified to address any claim amendments and new claim 81.
MPEP 2163.II.A.2.(a).i) states, “Whether the specification shows that applicant was in possession of the claimed invention is not a single, simple determination, but rather is a factual determination reached by considering a number of factors. Factors to be considered in determining whether there is sufficient evidence of possession include the level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention”.
For claims drawn to a genus, MPEP § 2163 states the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
According to MPEP 2163.II.A.3.(a).ii), [s]atisfactory disclosure of a ‘representative number’ depends on whether one of skill in the art would recognize that the applicant was in possession of the necessary common attributes or features possessed by the members of the genus in view of the species disclosed. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus…Instead, the disclosure must adequately reflect the structural diversity of the claimed genus, either through the disclosure of sufficient species that are ‘representative of the full variety or scope of the genus,’ or by the establishment of ‘a reasonable structure-function correlation.’"
The factors considered in the Written Description requirement are (1) level of skill and knowledge in the art, (2) partial structure, (3) physical and/or chemical properties, (4) functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the (5) method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient." MPEP § 2163.
The claims recite (in relevant part) a genus of Class 2 CRISPR-Cas endonucleases or nucleic acid encoding the endonucleases comprising RuvC or HEPN domains of the sequences disclosed in claims 1 and 81. As stated above, with the exception of the recited domain sequences in the claims, the remaining amino acid sequences of the genus of Class 2 CRISPR-Cas endonucleases are unlimited. In this case, the genus of recited Class 2 CRISPR-Cas endonucleases encompass species that are considered to be widely variant with respect to sequence.
The specification discloses the following representative species of the genus of Class 2 CRISPR-Cas endonucleases:
the Class 2 CRISPR-Cas endonucleases of SEQ ID NOs: 1-20.
Regarding the level of skill and knowledge in the art of amino acid modification, the reference of Singh et al. (Curr. Protein Pept. Sci. 18:1-11, 2017; cited on the attached Form PTO-892) reviews various protein engineering methods and discloses that despite the availability of an ever-growing database of protein structures and highly sophisticated computational algorithms, protein engineering is still limited by the incomplete understanding of protein functions, folding, flexibility, and conformational changes (see p. 7, column 1, top). Also, the unpredictability associated with residue substitution is exemplified by the reference of Zhang et al. (Structure 26:1474-1485, 2018; cited on the attached Form PTO-892), which discloses that even a substitution of a surface residue that was predicted to be benign caused significant structural changes and unexpected effects on the function of a polypeptide (p. 1475, column 1).
In view of the high level of unpredictability in the art of amino acid modification, because the genus of Class 2 CRISPR-Cas endonucleases is widely variant with respect to structure, and the specification discloses the actual reduction to practice of only 20 representative species among a widely variant genus, one of skill in the art would reasonably conclude that the disclosure fails to provide a representative number of species to describe the genus, and thus, that the applicant was not in possession of the recited genus of Class 2 CRISPR-Cas endonucleases. The claimed subject matter is not supported by an adequate written description because a representative number of species has not been described.
Response to Remarks: beginning on p. 18 of Applicant’s response to the rejection under 35 USC 112(a); Applicant in summary contends the amendment to claim 1 to recite the endonuclease contains domains sharing >90% sequence identity to the sequences disclosed in the claims obviates the rejection.
Applicant’s remarks are considered and found not convincing. As stated in the rejection above, the claimed system comprises a genus of Cas endonucleases that is structurally defined only by >90% sequence identity to the disclosed domains, wherein the disclosed domains comprise merely 12 amino acids in some cases. Aside from the domains recited in the claims, the amino acid sequence of the full polypeptide remains structurally unlimited, and therefore the genus is considered widely variant with respect to structure such that one of skill in the art would reasonably conclude that the applicant was not in possession of the recited genus of Class 2 CRISPR-Cas endonucleases.
Claim Rejections - 35 USC § 101
Claims 1, 4, 6, 71, 78-79 and 81 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more. Applicant’s attention is directed to the "Guidance for Determining Subject Matter Eligibility Of Claims Reciting Or Involving Laws of Nature, Natural Phenomena, & Natural Products”, released on December 16, 2014.
The instant rejection is maintained from the previous office action, and has been modified to address any claim amendments and new claim 81.
Claim Interpretation: The claims are drawn to an engineered system comprising a Class 2 CRISPR-Cas endonuclease or nucleic acid encoding the endonuclease, and a gRNA or nucleic acid encoding the gRNA, wherein the gRNA and endonuclease do not naturally occur together, wherein the gRNA is capable of hybridizing to a target sequence in a DNA or RNA sequence, and the gRNA is capable of forming a complex with the endonuclease. The endonuclease is further limited to containing a RuvC sequence or HEPN sequence of at least 90% identity to the sequences disclosed in claim 1.
As NCBI Accession No. NCU42495.1 (30 January 2020, 2 pages; cited on the attached Form PTO-892; herein NCBI2) discloses a type V Cas protein Cpf1 from the bacterium Candidatus Moraniibacteriota that has a sequence sharing 100% identity with SEQ ID NO: 75 [see Appendix A], the claims encompass the naturally occurring Cas protein of NCBI2.
The claims additionally recite “the gRNA and the Class 2 CRISPR-Cas endonuclease do not naturally occur together” and given a broadest reasonable interpretation, the claims encompass a combination of a recombinantly produced Class 2 CRISPR-Cas endonuclease and a naturally occurring gRNA, a combination of a naturally-occurring Class 2 CRISPR-Cas endonuclease and a recombinantly produced gRNA, and a combination of a recombinantly produced Class 2 CRISPR-Cas endonuclease and a recombinantly produced gRNA, wherein the recombinantly produced Class 2 CRISPR-Cas endonuclease and the recombinantly produced gRNA are structurally and functionally indistinguishable from the corresponding naturally occurring Class 2 CRISPR-Cas endonuclease and gRNA.
Claims 1, 4, 6, 71, and 78-79
Patent Eligibility Analysis Step 1: The claims are drawn to a composition of matter, which is one of the statutory categories of invention.
Patent Eligibility Analysis Step 2A Prong 1: The claims recite an engineered system comprising a CRISPR-Cas endonuclease and/or a gRNA that is structurally and functionally indistinguishable and not markedly different from the corresponding naturally occurring Class 2 CRISPR-Cas endonuclease and gRNA and thus the claimed system is considered to be a law of nature or natural phenomena (a natural product). Accordingly, claims 1, 4, 6, 71 and 78-79 are directed to a judicial exception.
Patent Eligibility Analysis Step 2A Prong 2: As noted above, claim 1 recites the limitation “the gRNA and the Class 2 CRISPR-Cas endonuclease do not naturally occur together.” This limitation, however, does not structurally and/or functionally distinguish the Class 2 CRISPR-Cas endonuclease and gRNA from than their naturally-occurring counterparts.
Claim 79 recites the additional element that one of the components of the system are lyophilized. As lyophilization is understood in the art to encompass a substance with substantial amounts of water removed and thereby does not change the structure of the substance, the characteristic of being lyophilized does not distinguish any of the components as markedly different than their naturally occurring counterparts.
There are no other additional elements recited in the claims beyond the judicial exception.
Patent Eligibility Analysis Step 2B: The claims only recite the judicial exception, without more and do not include any additional elements that could add significantly more to the judicial exception.
As such, the claims do not qualify as eligible subject matter. For these reasons the claim is rejected under section 101 as being directed to non-statutory subject matter.
Claim 81
Patent Eligibility Analysis Step 1: The claim is drawn to a composition of matter, which is one of the statutory categories of invention.
Patent Eligibility Analysis Step 2A Prong 1: The claim recites an engineered system comprising a CRISPR-Cas endonuclease and/or a gRNA that is structurally and functionally indistinguishable and not markedly different from the corresponding naturally occurring Class 2 CRISPR-Cas endonuclease and gRNA and thus the claimed system is considered to be a law of nature or natural phenomena (a natural product). Accordingly, claim 81 is directed to a judicial exception.
Patent Eligibility Analysis Step 2A Prong 2: As noted above, claim 81 recites the limitation “the gRNA and the Class 2 CRISPR-Cas endonuclease do not naturally occur together.” This limitation, however, does not structurally and/or functionally distinguish the Class 2 CRISPR-Cas endonuclease and gRNA from than their naturally-occurring counterparts.
There are no other additional elements recited in the claims beyond the judicial exception.
Patent Eligibility Analysis Step 2B: The claims only recite the judicial exception, without more and do not include any additional elements that could add significantly more to the judicial exception.
As such, the claims do not qualify as eligible subject matter. For these reasons the claim is rejected under section 101 as being directed to non-statutory subject matter.
Response to Remarks: beginning on p. 21 of Applicant’s response to the rejection under 35 USC 101; Applicant in summary contends the limitation that the endonuclease and the gRNA do not naturally occur together distinguishes the system from its naturally occurring counterpart, providing a functionally distinct activity of the claimed system; Applicant further contends the claimed system should be considered integrated into practical application at Step 2A Prong 2 based on the functionality of the endonuclease with the gRNA, as this activity would allow the Cas to cleave a unique target other than what would be found in nature.
Applicant’s remarks are considered and found not convincing. As stated in the rejection above, the limitation wherein the endonuclease and the gRNA do not occur naturally together does not establish any structural characteristics of the claimed endonuclease and gRNA that distinguish the claimed endonuclease and gRNA from naturally-occurring counterparts. Additionally, this limitation encompasses (1) a combination of a recombinantly produced Class 2 CRISPR-Cas endonuclease and a naturally occurring gRNA, (2) a combination of a naturally-occurring Class 2 CRISPR-Cas endonuclease and a recombinantly produced gRNA, and (3) a combination of a recombinantly produced Class 2 CRISPR-Cas endonuclease and a recombinantly produced gRNA, wherein the recombinantly produced Class 2 CRISPR-Cas endonuclease and the recombinantly produced gRNA are structurally and functionally indistinguishable from the corresponding naturally occurring Class 2 CRISPR-Cas endonuclease and gRNA. The only structural component provided by the claim is the sequence homology to a domain of the endonuclease, which encompasses a naturally occurring Cas endonuclease of NCBI2.
Regarding Applicant’s assertion that the functionality of the system is not natural, the functional aspects of the system are considered inherent to the structure of its components, in this case the polypeptide sequence of the Cas endonuclease and the nucleic acid sequence of the gRNA. As the claimed polypeptide sequence of the Cas endonuclease encompasses a naturally occurring Cas endonuclease, and the nucleic acid sequence of the gRNA is undefined, the claimed system encompasses a naturally occurring Cas endonuclease and its corresponding gRNA, which would be expected to have the same functionality of cleaving target nucleic acid. As the target of the cleavage is determined by the gRNA sequence, and the gRNA sequence is undefined, there is no functionality implied by the claims that is markedly different from the naturally occurring counterpart components of the system, as well as no structure that is markedly different from the naturally occurring counterpart components of the system.
Regarding Applicant’s assertion that the claimed system should be considered integrated into practical application at Step 2A Prong 2 based on the functionality of the endonuclease with the gRNA, the assessment of additional elements and whether they integrate the JE into a practical application is carried out with Abstract Idea 101 rejections in the determination of whether the recited additional elements integrate the abstract idea into a practical application and therefore amount to significantly more than the JE. As the instant application is drawn to a product, and is identified as drawn to a natural product JE, the assessment of additional elements in Step 2A Prong 2 is carried out to determine if these additional elements provide any characteristics that would make the claimed invention markedly different from its naturally occurring counterpart. Product claims are evaluated based on structural characteristics, such as the sequence homology to domains of a Cas endonuclease recited in the claim. The functional limitations cited by applicant in the remarks do not impart any structural limitations on the claimed system, and as written, the claimed system encompasses naturally occurring systems of Cas endonucleases and gRNA that are not markedly different from naturally occurring counterparts.
Claim Rejections - 35 USC § 103
The rejection of claims 1, 4, 6, 71 and 78 under 35 U.S.C. 103 as being unpatentable over Cheng et al. (US 2019/0002889; cited on the Form PTO-892 mailed 02/24/2025; herein Cheng) in view of NCBI Accession No. WP_003034647.1 (2 pages, 2019; cited on the Form PTO-892 mailed 02/24/2025), and
the rejection of claims 79-80 under 35 U.S.C. 103 as being unpatentable over Cheng and NCBI1, and further in view of Broughton et al. (Nat Biotechnol, 2020, 38:870; cited on the Form PTO-892 mailed 02/24/2025; herein Broughton)
are withdrawn in view of the amendment to claim 1 to recite “or a sequence comprising at least 90% identity thereto” in reference to the sequence of the RuvC domains of the claimed endonuclease.
Claims 1, 4, 6, 71, 78 and 81 are newly rejected under 35 U.S.C. 103 as being unpatentable over Cheng in view NCBI Accession No. NCU42495.1 (30 January 2020, 2 pages; cited on the attached Form PTO-892; herein NCBI2).
The instant rejection is necessitated by claim amendment.
Claim 1 is drawn to an engineered system comprising
(a) a Class 2 CRISPR-Cas endonuclease or a nucleic acid encoding the endonuclease, wherein the Class 2 CRISPR-Cas endonuclease is
(i) a Class 2 Type II CRISPR-Cas endonuclease comprising at least one of the RuvC or HNH sequences SEQ ID NOs: 116-118, 121-123, 126-128, 131-133, or 138-141, or a sequence comprising at least 90% sequence identity thereto;
(ii) a Class 2 Type V CRISPR-Cas endonuclease comprising at least one of the RuvC sequences of SEQ ID NOs: 62-64, 67-69, 71-73, 75-77, 80-82, 85-87, 89-91, or 135-137, or a sequence comprising at least 90% sequence identity thereto; or
(iii) a Class 2 Type VI CRISPR-Cas endonuclease comprising at least one of the HEPN sequences of SEQ ID NOs: 94-95, 97, 99-100, 102, 104-105, 107-108, 110-111 or 113, or a sequence comprising at least 90% sequence identity thereto, and
(b) a gRNA or a nucleic acid encoding the gRNA, wherein the gRNA and the Class 2 CRISPR-Cas endonuclease do not naturally occur together, wherein the gRNA is capable of hybridizing to a target sequence in a target DNA or RNA, and the gRNA is capable of forming a complex with the Class 2 CRISPR-Cas endonuclease.
Cheng discusses novel CRISPR RNA targeting systems [title], and describes systems for the manipulation of nucleic acids in a targeted fashion using non-naturally occurring engineered CRISPR systems and components [abstract].
Regarding claims 1, 6, and 81 and the limitation of a Class 2 CRISPR-Cas endonuclease, Cheng discloses a system comprising an RNA guide capable of hybridizing to a target nucleic acid and a non-naturally occurring CRISPR-associated (Cas) protein capable of binding to the RNA guide [para 0010], wherein the Cas protein is a Class 2 CRISPR-Cas protein selected from the group consisting of a Type VI, Type V and Type II Cas protein [para 0017]. The gRNA recited in the claim is understood to be a guide RNA, and as the Cas protein is non-naturally occurring, it is understood that the Cas and the gRNA do not naturally occur together.
Cheng does not teach a Type V Cas protein comprising at least one of the RuvC sequences of the claims.
NCBI2 discloses a type V Cas protein Cpf1 from the bacterium Candidatus Moraniibacteriota that has a sequence sharing 100% identity with SEQ ID NO: 75 [see Appendix A].
In view of Cheng and NCBI2, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the system of Cheng by using the endonuclease of NCBI2 to arrive at the claimed invention, since the simple substitution of one known element for another results in a predictable result. One of ordinary skill in the art would have recognized that the Type V Cas protein of Cheng and the endonuclease of NCBI2 are both Type V Cas proteins, and as such one would have predicted that both are capable of being incorporated into such a system as described by Cheng. Thus it would have been obvious to one of ordinary skill in the art to replace the Type V Cas protein of Cheng with the Type V Cas protein of NCBI2, as one of ordinary skill in the art would have been able to carry out such a substitution with a reasonable expectation of success because both Cheng and NCBI2 relate to Type V Cas proteins.
Regarding claim 4, Cheng discloses a vector which includes multiple nucleic acids, each encoding a component of a Cas system described herein [para 0210], wherein the gRNA is considered a component of the Cas system as described above, and the encoding of a gRNA on a single nucleic acid encompasses a single-molecule gRNA as recited in the claims.
Regarding claim 71, Cheng discloses the incubation of effectors, corresponding to the Cas protein, with pre-crRNAs, corresponding to gRNAs, for a cleavage assay in a buffer of 20 mM Tris, pH 8.0 held at 37 °C for 10 minutes [para 0365]. As the instant specification does not define a stabilizing buffer, the 20 mM Tris buffer of Cheng is considered to correspond to a stabilizing buffer, and therefore the combination of Cas, gRNA and buffer as disclosed by Cheng is considered to correspond to the composition recited in the claim.
Regarding claim 78, in light of the combined system of Cheng and NCBI1 as described above, it would have been obvious for one of skill in the art to combine each of the components disclosed in the rejection of claim 1 into a kit for convenience.
Therefore, the invention of claims 1, 4, 6, 71, 78 and 81 would have been obvious to one of ordinary skill in the art before the effective filing date.
Claims 79-80 are newly rejected under 35 U.S.C. 103 as being unpatentable over Cheng and NCBI2 as applied to claims 1, 4, 6, 71, 78 and 81 above, and further in view of Broughton.
The instant rejection is necessitated by claim amendment.
Claim 79 is drawn to the kit of claim 78, wherein one or more components are lyophilized.
The teachings of Cheng and NCBI2 as applied to claims 1, 4, 6, 71, 78 and 81 are described above. These references do not teach lyophilized components.
Broughton discusses CRISPR-Cas12-based detection of SARS-CoV-2 [title], and describes CRISPR-based lateral flow assays for that are rapid, accurate, and easy-to-implement for the detection of SARS-CoV-2 from respiratory swab RNA extracts [abstract].
Regarding claim 79, Broughton teaches the use of a system comprising CRISPR-Cas12, gRNA and a target RNA derived from nasopharyngeal swabs to detect the presence of SARS-CoV-2 [Figure 1d], and teaches that the lyophilization of reagents from the system could enable point-of-care testing outside of the clinical diagnostic laboratory, such as airports, local emergency departments and clinics, and other locations [p 874, col 1, final paragraph].
In view of Broughton, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the combined system of Cheng and NCBI2 by lyophilizing the components, as taught by Broughton, to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to modify the combined system of Cheng and NCBI2, because Broughton teaches that systems for rapid, accurate, and easy-to-implement detection of SARS-CoV-2 from RNA extracts could be improved and applied to point-of-care diagnostics by lyophilizing the system components. One of ordinary skill in the art would have had a reasonable expectation of success because Cheng and Broughton relate to systems comprising CRISPR-Cas proteins and gRNAs.
Regarding claim 80, Broughton teaches the system comprising CRISPR-Cas12, gRNA and a target RNA derived from nasopharyngeal swabs to detect the presence of SARS-CoV-2 in the presence of a labeled reporter [Figure 1d], wherein the gRNA is understood to be directed towards SARS-CoV-2.
Therefore, the invention of claims 79-80 would have been obvious to one of ordinary skill in the art before the effective filing date.
Response to Remarks: beginning on p. 24 of Applicant’s response to rejections under 35 USC 103; Applicant in summary contends there is no teaching, suggestion or motivation to combine Cheng and NCBI1, nor a reasonable expectation of success.
Applicant’s remarks are considered and found not convincing. As stated above, the claims are considered obvious in view of Cheng and NCBI2 based on the rationale of simple substitution, which does not require a teaching, suggestion or motivation to combine (see MPEP 2143.I.B). Additionally, as stated in the rejection above, the simple substitution of one known element for another results in a predictable result, and as one of ordinary skill in the art would have recognized that the Type V Cas protein of Cheng and the endonuclease of NCBI2 are both Type V Cas proteins, one would have predicted that both are capable of being incorporated into such a system as described by Cheng, and thus it would have been obvious to one of ordinary skill in the art to replace the Type V Cas protein of Cheng with the Type V Cas protein of NCBI2, and one of ordinary skill in the art would have been able to carry out such a substitution with a reasonable expectation of success because both Cheng and NCBI2 relate to Type V Cas proteins.
Allowable Subject Matter
The closest prior art of record to claims 82-87, and to the limitation of “the Class 2 Type V CRISPR-Cas endonuclease comprises any one of SEQ ID NOs: 1-7 or 20, or a sequence comprising at least 90% sequence identity thereto” in claim 10, is considered to be NCBI Accession No. WP_003034647.1 (2 pages, 2019; cited on the Form PTO-892 mailed 02/24/2025), which discloses a Type V CRISPR-associated protein Cas12a/Cpf1 from Francisella tularensis [title] that shares 46.1% sequence identity with SEQ ID NO: 1 [see Appendix B]. There is no teaching or suggestion in the prior art of record of a Class 2 CRISPR-Cas endonuclease or a nucleic acid encoding the endonuclease, wherein the Class 2 CRISPR-Cas endonuclease comprises SEQ ID NOs: 1-7 or 20, or 90% sequence identity thereto.
The teachings of NCBI alone or in combination with the other prior art of record do not teach or suggest:
the limitation of “the Class 2 Type V CRISPR-Cas endonuclease comprises any one of SEQ ID NOs: 1-7 or 20, or a sequence comprising at least 90% sequence identity thereto” in claim 10,
an engineered system comprising (a) a Class 2 CRISPR-Cas endonuclease or a nucleic acid encoding the endonuclease; and (b) a gRNA or a nucleic acid encoding the gRNA, wherein the gRNA and the Class 2 CRISPR-Cas endonuclease do not naturally occur together, wherein the gRNA is capable of hybridizing to a target sequence in a target DNA or RNA, and the gRNA is capable of forming a complex with the Class 2 CRISPR-Cas endonuclease, and wherein the Class 2 CRISPR-Cas endonuclease comprises SEQ ID NOs: 1-7 or 20, or 90% sequence identity thereto as recited in claim 82, or
an engineered system comprising (a) a Class 2 CRISPR-Cas endonuclease or a nucleic acid encoding the endonuclease; and (b) a gRNA or a nucleic acid encoding the gRNA, wherein the gRNA and the Class 2 CRISPR-Cas endonuclease do not naturally occur together, wherein the gRNA is capable of hybridizing to a target sequence in a target DNA or RNA, and the gRNA is capable of forming a complex with the Class 2 CRISPR-Cas endonuclease, and wherein the Class 2 CRISPR-Cas endonuclease comprises SEQ ID NOs: 1-7 or 20 as recited in claim 83.
Therefore claims 10 and 82-87 are allowable over the prior art of record.
Conclusion
Status of the Application:
Claims 1-19, 62-69, 71, and 74-87 are pending.
Claims 2-3, 5, 7-9, 11-19, 62-69 and 74-77 are withdrawn.
Claims 1, 4, 6, 71 and 78-81 are rejected.
Claim 10 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.
Claim 82 is objected to for a minor informality and claims 84-87 are objected to for being dependent upon an objected claim.
Claim 83 is in condition for allowance.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOSEPH SPANGLER whose telephone number is (571)270-0314. The examiner can normally be reached M-F 7:30 am - 4:30 pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Manjunath Rao can be reached at (571) 272-0939. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JOSEPH R SPANGLER/
Examiner
Art Unit 1656
/David Steadman/Primary Examiner, Art Unit 1656
APPENDIX A
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142
675
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Sequence alignment of SEQ ID NO: 75 with NCBI Accession No. NCU42495.1 (reference NCBI2).
APPENDIX B
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399
645
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Sequence alignment of SEQ ID NO: 1 with NCBI Accession No. WP_00303467.1 (reference NCBI1).