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 .
Notice of New Examiner
The Examiner would like to note for the Applicant that this case has been
transferred to a new examiner for examination. Any further communications on this case may be directed to the contact information included in the conclusion of this
office action.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on September 1st, 2023 is acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner.
However, it is noted by the examiner that the reference “R. FAN ET AL. "Shortening the sgRNA-DNA interface enables SpCas9 and eSpCas9(1.1) to 59 ick the target DNA strand" 1-2. Science China. 24 June 2020.” does not appear to have a corresponding document filed. Therefore, it has not been considered and is lined through.
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Election/Restrictions
Applicant’s election without traverse of Group 2, claims 23-24, in the reply filed on February 18th, 2026 is acknowledged.
It is noted that the Applicant has cancelled claims 2-17 and added claims 62-77. Claims 62-77 ultimately depend from claim 23 and are therefore included as a part of the elected Group 2.
It is further noted that the Applicant has requested reconsideration of the restriction, arguing that the multiple groups can be searched and examined together without undue burden. However, the Applicant is reminded that the claims were restricted under lack of unity, which does not depend on indicating an undue search burden. Given that the Groups of inventions have been shown to have a lack of unity, both in the art as presented in the restriction requirement and in the art as presented in the below rejections, the special technical feature shared between claims 1, 23, and 46 does not make a contribution over the prior art. Therefore, the restriction requirement is maintained. Because applicant did not distinctly and specifically point out the appropriate errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 1 and 46 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on February 18th, 2026.
Claim Summary
Claims 2-22, 25-45, and 47-61 have been canceled. Claims 62-77 have been added. Claims 1, 23-24, 46 and 62-77 are pending. Claims 1 and 46 are withdrawn from consideration as being drawn to a non-elected invention/species. Claims 23-24 and 62-77 are under examination and discussed in this Office action.
Nucleotide and/or Amino Acid Sequence Disclosures
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter “Legal Framework”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
Specific deficiency - Sequences appearing in the specification are not identified by sequence identifiers (i.e., “SEQ ID NO:X” or the like) in accordance with 37 CFR 1.831(c). This includes all sequences in Table 1, starting at page 80 of the substitute specification filed April 30th, 2024, and all sequences in Table 2, starting at page 132 of the substitute specification filed April 30th, 2024. The Applicant should review the entire specification for other instances of sequences that may be missing an associated sequence identifier.
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required sequence identifiers, consisting of:
• A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
• A copy of the amended specification without markings (clean version); and
• A statement that the substitute specification contains no new matter.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (see pages 28 and 76 of the substitute specification filed April 30th, 2024). Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
The use of terms such as ATTO550 and Cy5, which are trade names or marks used in commerce, have been noted in this application. The terms should be accompanied by the generic terminology; furthermore, the terms should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks. Applicant is advised to review the specification for any other possible trademarks other than those indicated above.
Claim Objections
Applicant is advised that should claim 24 be found allowable, claim 62 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Claim Rejections - 35 USC § 112(d)
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 63 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, or for failing to include all the limitations of the claim upon which it depends. Claim 63 recites the limitation “wherein the genomic nucleic acid sequences comprise genomic DNA”. However, claim 23, from which claim 63 depends, already claims genomic DNA. Therefore, claim 63 fails to further limit the subject matter of the claim upon which it depends 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.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 23-24 and 62-77 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 23, 24, and 62 all recite the limitation "the specific nucleic acid of interest". There is insufficient antecedent basis for this limitation in the claim. There is no introduction of “a specific nucleic acid of interest” in claim 23, which is required to establish antecedent basis for the phrase in all three claims. Therefore, the claims are found indefinite. Claims 63-77 are also rejected here for their dependence back to claim 23 and not further clarifying the identified issue.
Claim 23 also recites “a method of detecting mutations in a genome of a cell or tissue”, followed later by “contacting the denatured DNA with a detectably labeled probe, wherein the detectably labeled probe is complementary to the specific nucleic acid sequence of interest”, and finally “detecting the mutations in the genome”. It is unclear from this recitation how multiple mutations would be able to be detected when the probe as claimed appears to be directed to a single specific nucleic acid of interest. Given the plurality of “mutations”, this would suggest that multiple specific nucleic acids of interest are being detected. This contradicts the single probe and the specific nucleic acid sequence of interest that is claimed, and also contradicts claim language in dependent claims that is also directed to “the specific nucleic acid of interest”. In other words, it is unclear if a single sequence of interest is meant to be detected or multiple sequences of interest are meant to be detected. Therefore, the claim is found indefinite. For the purpose of compact prosecution, and given the further claim language indicative of a single sequence of interest, it is interpreted that there is a single mutation/a single specific nucleic acid sequence of interest detected by the method. Claims 24 and 62-77 are also rejected here for their dependence back to claim 23 and not further clarifying the identified issue.
Claim 24 recites the limitation “wherein the specific nucleic acid sequence of interest comprises one or more nucleic acid sequences in coding and non-coding nucleic acid sequences of the genome”. It is unclear from this recitation how more than one sequence can comprise “the” (i.e., a single) specific nucleic acid sequence. Referencing “the” specific nucleic acid sequence indicates that one sequence is of interest, without the option for there to be more. This is further complicated by the issues noted for claim 23 regarding the claim language referring to both a single sequence and multiple sequences. Therefore, the claim is found indefinite. For the purpose of compact prosecution, it is interpreted that the specific nucleic acid sequence of interest comprises one nucleic acid sequence. Given that claim 62 is a duplicate of claim 24, the same issue is noted. Claims 63 and 74 are also rejected here for their dependence upon claim 62 and not further clarifying the identified issue.
Claim 63 recites the limitation "the genomic nucleic acid sequences". There is insufficient antecedent basis for this limitation in the claim. Claim 74 is also rejected here for its dependence on claim 63 and not further clarifying the identified issue.
Claim 67 recites the limitation “wherein the gene editing complex comprises at least two guide nucleic acid sequences”. It is unclear from this recitation what “at least two guide nucleic acid sequences” refers to. For instance, as indicated in Zhang (WO 2016028682 A1), Cas proteins form complexes with a crRNA and a tracrRNA, which are components of a guide RNA (Pages 2-3, paragraph [0008]). The crRNA and the tracrRNA would reasonably comprise at least two guide nucleic acid sequences. However, this recitation may also be referring to at least two complete guide RNAs instead. If this option were to be the case, it would further be unclear how the gene editing complex would comprise at least two guide nucleic acid sequences given that Cas proteins interact with one guide RNA, as exemplified in Figure 1 of Zhang. Therefore, the claim is found indefinite. For the purpose of compact prosecution, the at least two guide nucleic acid sequences will be interpreted as a crRNA and a tracrRNA.
Claim 68 recites the limitation "the one or more guide nucleic acid sequences". There is insufficient antecedent basis for this limitation in the claim. Furthermore, it is unclear from this recitation what one or more guide nucleic acid sequences may be referring to. As has been noted for claim 67 above, there are conflicting interpretations for this recitation, including that a crRNA and tracrRNA would reasonably comprise one or more guide nucleic acid sequences or that two complete guide RNAs would reasonably comprise one or more guide nucleic acid sequences. Therefore, the claim is found indefinite. Claims 69-72 are also rejected here for their dependence on claim 68 and not further clarifying the identified issue.
Claim 69 recites the limitation “wherein the guide RNA (gRNA) sequences comprise at least about 90% sequence identity to one or more target nucleic acid sequences in coding and non-coding nucleic acid sequences of the genome, or complementary sequences thereof”. It is unclear from this recitation how more than one target nucleic acid sequence is involved in the method as claimed given the issues noted for claim 23 regarding the claim language referring to both a single sequence and multiple sequences. Therefore, the claim is found indefinite. For the purpose of compact prosecution, it is interpreted that the one or more target nucleic acid sequences comprises just one target nucleic acid sequence. The same issue is noted for claim 70.
Claim 69 is also indefinite in the recitation “at least about.” The phrase “at least” typically indicates a minimum point; however, the phrase “at least” is controverted by the term “about,” which implies that values above and below the indicated amount are permitted. Therefore, the juxtaposition of these two terms makes it unclear what minimum sequence identity is encompassed by the claim. In Amgen, Inc. v. Chugai Pharmaceutical co., 927 F.2d 1200 (CAFC 1991), the CAFC stated, “[t]he district court held claims 4 and 6 of the patent invalid because their specific activity of “at least about 160,000” was indefinite.” After review, the CAFC states “[w]e therefore affirm the district court’s determination on this issue.” Thus, the CAFC found the phrase “at least about” indefinite where the metes and bounds of the term were not defined in the specification. See MPEP 2173.05(b) III. For the purpose of compact prosecution, at least about 90% will be interpreted as at least 90%.
Claims 69 and 70 recites the limitation "wherein the guide RNA (gRNA) sequences". There is insufficient antecedent basis for this limitation in the claims.
Claim 73 recites the limitation "the guide RNA". There is insufficient antecedent basis for this limitation in the claim. Therefore, the claim is found indefinite.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
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 23, 63-68, 71, and 73-77 are rejected under 35 U.S.C. 103 as being unpatentable over Peter (US 20110039716 A1), in view of Zhang (WO 2016028682 A1) and Korfhage (US 20130210019 A1).
Regarding instant claim 23, Peter teaches a method of detecting mutations in a genome of a cell or tissue, comprising: inducing a nick in genomic DNA by an endonuclease (Page 4, paragraph [0040]); denaturing the genomic DNA by contacting the genome with a site-specific endonuclease (Page 4, paragraph [0040]); contacting the denatured genomic DNA with a detectably labeled probe, wherein the detectably labeled probe is complementary to the specific nucleic acid sequence of interest (Page 4, paragraph [0040]); and, detecting the mutations in the genome (Page 4, paragraph [0040]) (see 112(b) interpretation).
Peter does not teach inducing a nick in genomic DNA by a gene editing complex. Peter also does not teach denaturing using a helicase enzyme on nicked DNA.
Zhang, in a reasonably pertinent field, teaches a gene editing complex comprising a CRISPR complex (Page 5, paragraph [0017]: “The CRISPR complex of the invention provides an effective means for modifying a target polynucleotide”). Zhang further teaches the CRISPR enzyme of the CRISPR complex is a nickase, where the nickase is a modified Cas9 protein (Pages 5-6, paragraph [0019]).
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 method of Peter with the gene editing complex of Zhang. Since Zhang teaches on Cas9 nickases, which is reasonably pertinent to the method of Peter, 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 systems do not require the generation of customized proteins to target specific sequences. Instead, a single Cas enzyme can be programmed by a short RNA molecule to recognize a specific DNA target (Zhang, Pages 4-5, paragraph [0015]).
Korfhage, in a reasonably pertinent field, teaches that genomic DNA can be denatured using a helicase enzyme on DNA nicked by an endonuclease (Page 1, paragraph [0003]: “HDA is based on the ability of helicases to unwind double-stranded nucleic acids, particularly DNA, without the need for heating or even thermocycling. In HDA, the separated DNA strands are replicated using DNA polymerases and suitable oligonucleotide primers.”; Page 1, paragraph [0010]: “HDA amplification method that is performed in the presence of a nicking endonuclease”; Page 2, paragraph [0038]: Genomic DNA).
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 method of Peter with the helicase of Korfhage. Since Korfhage teaches on using endonuclease nicked DNA unwound by helicase, which is reasonably pertinent to the method of Peter, 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 helicases unwind double-stranded DNA without the need for heating (Korfhage, Page 1, paragraph [0003]).
Regarding instant claim 63, Peter, in view of Zhang and Korfhage, teaches the method of claim 62. Peter further teaches wherein the genomic nucleic acid sequences comprise genomic DNA (Page 4, paragraph [0040]).
Regarding instant claim 64, Peter, in view of Zhang and Korfhage, teaches the method of claim 23. Zhang further teaches wherein the nicking of genomic DNA sequences by the gene editing complex produces a 3' single-stranded nucleic acid overhang (Pages 5-6, paragraph [0019]).
Regarding instant claim 65, Peter, in view of Zhang and Korfhage, teaches the method of claim 64. Korfhage further teaches wherein the helicase binds to the genomic DNA at the site of the nick and unwinds downstream double stranded genomic DNA (Page 1, paragraph [0003]).
Regarding instant claim 66, Peter, in view of Zhang and Korfhage, teaches the method of claim 23. Zhang further teaches wherein the gene editing complex comprises a Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)-associated endonuclease and at least one guide nucleic acid sequence (Page 5, paragraph [0017]).
Regarding instant claim 67, Peter, in view of Zhang and Korfhage, teaches the method of claim 23. Zhang further teaches wherein the gene editing complex comprises at least two guide nucleic acid sequences (Pages 2-3, paragraph [0008]; see 112(b) interpretation) .
Regarding instant claim 68, Peter, in view of Zhang and Korfhage, teaches the method of claim 23. Zhang further teaches wherein the one or more guide nucleic acid sequences are RNA (Pages 2-3, paragraph [0008]; see 112(b) interpretation).
Regarding instant claim 71, Peter, in view of Zhang and Korfhage, teaches the method of claim 68. Zhang further teaches one or more guide RNAs having one or more nucleotide mismatches compared to the target nucleic acid sequence, or complementary sequences thereof (Page 3, paragraph [0011]).
Regarding instant claim 73, Peter, in view of Zhang and Korfhage, teaches the method of claim 23. Zhang further teaches wherein the guide RNA comprises crRNA and tracrRNA (Pages 2-3, paragraph [0008]).
Regarding instant claim 74, Peter, in view of Zhang and Korfhage, teaches the method of claim 63. Zhang further teaches wherein the gene-editing complex comprises CRISPR-associated endonuclease is a Type II Cas endonuclease (Pages 2-3, paragraph [0008]: Type II is Cas9; Pages 5-6, paragraph [0019]).
Regarding instant claims 75 and 76, Peter, in view of Zhang and Korfhage, teaches the method of claim 66. Zhang further teaches wherein the CRISPR-associated endonuclease is a variant of Cas9 endonuclease (Pages 5-6, paragraph [0019]: nickase is a modified Cas9).
Regarding instant claim 77, Peter, in view of Zhang and Korfhage, teaches the method of claim 76. Zhang further teaches wherein the Cas9 nuclease is a Staphylococcus aureus Cas9 nuclease (Pages 5-6, paragraph [0019]).
Claims 24, 63, and 69-70 are rejected under 35 U.S.C. 103 as being unpatentable over Peter (US 20110039716 A1), Zhang (WO 2016028682 A1) and Korfhage (US 20130210019 A1), as applied to claims 23, 63-68, 71, and 73-77, and further in view of Jarosz (US 20160281138 A1).
Regarding instant claims 24 and 62, Peter, in view of Zhang and Korfhage, teaches the method of claim 23.
None of these references teach wherein the specific nucleic acid sequence of interest comprises one or more nucleic acid sequences in coding and non-coding nucleic acid sequences of the genome.
Jarosz, in a reasonably pertinent field, teaches wherein nucleic acid sequences of interest include, in any combination, exons and introns, which have nucleic acid based baits designed to hybridize to the combination of exons and introns (Page 14, paragraph [0099]). This reasonably teaches one or more nucleic acid sequences in coding and non-coding nucleic acid sequences of the genome (also see 112(b) interpretation).
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 method of Peter, in view of Zhang and Korfhage, with the nucleic acids of interest of Jarosz. Since Jarosz teaches on nucleic acid based detection, which is reasonably pertinent to Peter, in view of Zhang and Korfhage, 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 detection nucleic acids are directed to particular sequences in targeted regions of the genome based on the presence or absence of informative SNPs (Page 14, paragraph [0098]).
Regarding instant claims 69 and 70, Peter, in view of Zhang and Korfhage, teaches the method of claim 68. Zhang teaches a guide sequence is a polynucleotide sequence having sufficient complementarity with a target polynucleotide to hybridize and direct binding of a CRISPR complex to the target (Page 135, paragraph [00419]). Zhang teaches the degree of complementarity may be 90% or more (e.g. 90% sequence identity or more; Page 135, paragraph [00419]; see 112(b) interpretation).
None of these references teach one or more target nucleic acid sequences in coding and non-coding nucleic acid sequences of the genome, or complementary sequences thereof.
Jarosz, in a reasonably pertinent field, teaches wherein nucleic acid sequences of interest include, in any combination, exons and introns, which have nucleic acid based baits designed to hybridize to the combination of exons and introns (Page 14, paragraph [0099]). This reasonably teaches one or more target nucleic acid sequences in coding and non-coding nucleic acid sequences of the genome (also see 112(b) interpretation).
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 method of Peter, in view of Zhang and Korfhage, with the nucleic acids of interest of Jarosz. Since Jarosz teaches on nucleic acid based detection, which is reasonably pertinent to Peter, in view of Zhang and Korfhage, 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 detection nucleic acids are directed to particular sequences in targeted regions of the genome based on the presence or absence of informative SNPs (Page 14, paragraph [0098]).
Claim 72 is rejected under 35 U.S.C. 103 as being unpatentable over Peter (US 20110039716 A1), Zhang (WO 2016028682 A1) and Korfhage (US 20130210019 A1), as applied to claims 23, 63-68, 71, and 73-77, and further in view of Zheng (Profiling single-guide RNA specificity reveals a mismatch sensitive core sequence, Scientific Reports, January 2017, 7, 1-8).
Regarding instant claim 72, Peter, in view of Zhang and Korfhage, teaches the method of claim 71.
It is first 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. It is also noted that a “wherein” clause, such as that in claim 71, must give “meaning and purpose to the manipulative steps.” See, MPEP § 2111.04. The claimed “wherein one or more single-nucleotide mismatches in one or more guide RNAs inhibit nicking of target genomic DNA” does not serve to add meaning and purpose to the manipulative steps because it does not further limit the method as claimed. Therefore, the rejection of claim 71 can also be said to sufficiently reject claim 72. However, in the interest of compact prosecution, the quoted recitation is also addressed in the art below.
Peter, Zhang, and Korfhage do not teach wherein one or more single-nucleotide mismatches in one or more guide RNAs inhibit nicking of target genomic DNA.
Zheng, in a reasonably pertinent field, teaches that mismatches at particular positions of guide RNAs nearly abolishes cleavage activity of CRISPR-Cas9 (Page 5, 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 method of Peter, in view of Zhang and Korfhage, with the mismatches of Zheng. Since Zheng teaches on Cas9 cleavage abilities given guide RNA mismatches, which is reasonably pertinent to Peter, in view of Zhang and Korfhage, 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 mismatches reduce off-target cleavage (Zheng, Page 5, paragraph 6).
Conclusion
All claims stand rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Allison E Schloop whose telephone number is (703)756-4597. The examiner can normally be reached Monday-Friday 8:30-5 ET.
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/ALLISON E SCHLOOP/Examiner, Art Unit 1683
/Robert T. Crow/Primary Examiner, Art Unit 1683
Prosecution Insights