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 .
Election/Restrictions
Applicant’s election of invention I, claims 1-5, drawn to a method of treating an organism for a disease caused by an infectious agent, in the reply filed on 12/02/2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 6-10 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 10/02/2025.
Status of Claims
Claims 1-10 are currently pending.
Claims 1-5 are under consideration, as claims 6-10 are withdrawn.
Priority
The present application and all claims are being examined with an effective filing date of July 19, 2023.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (e.g., para 0047 and 0076). 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.
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 1-5 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 1 is indefinite due to the recitation of “at least one protein necessary for performance of a function the infectious agent requires for survival” because there is no objective criteria or standard for determining what constitutes a protein that is “necessary”, nor does it define what type of “performance of a function” is required, what the context for “survival” is, or how such necessity is evaluated. As currently presented, it is unclear whether a protein that merely contributes to, is involved in, or affects any function that relates to survival in any condition would meet the limitation. For examination purposes, the examiner is interpreting “at least one protein necessary for performance of a function the infectious agent requires for survival” as encompassing proteins that are required for growth, reproduction, metabolism or maintenance of structural integrity, as well as proteins required for survival of the infectious agent under particular environmental and therapeutic conditions, including conditions in which the infectious agent is exposed to antibiotic treatment, such that the loss or disruption of the protein, or gene encoding said protein, would compromise survival.
Claim 1 is further indefinite because it recites “determining, in each gene, at least one exon arrangement that can produce the mRNA” without clarifying what constitutes an “exon arrangement” or how such an arrangement is determined. This is especially the case wherein the claim encompasses bacterial infectious agents, which do not undergo exon–intron splicing. As a result, it is unclear how this limitation applies to the claimed embodiments, rendering the scope of the claim uncertain. For examination purposes, the examiner is interpreting the term “exon arrangement” as referring to a defined organization or combination of exonic nucleotide sequences within a gene that, when transcribed, gives rise to a particular mRNA transcript, in organisms that undergo exon-intron splicing.
Dependent claims 2-5 are included in this rejection as they fail to remedy the indefiniteness noted above.
Clarification for all of the above is required.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-5 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, 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, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
It is noted that MPEP 2111.01 states that ''[d]uring examination, the claims must be interpreted as broadly as their terms reasonably allow. Claim 1 has been broadly interpreted as a genus of methods for treating a genus of organisms for a genus of diseases caused by a genus of infectious agents, wherein a genus of “essential genes” of the infectious agent are identified, targeted using a guide RNA and nuclease complex, and inactivated so as to treat the disease in the organism.
MPEP 2163 I. states that to “satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention.
MPEP 2163. II.A.3.(a) states that “Possession may be shown in many ways. For example, possession may be shown by describing an actual reduction to practice of the claimed invention. Possession may also be shown by a clear depiction of the invention in detailed drawings or in structural chemical formulas which permit a person skilled in the art to clearly recognize that inventor had possession of the claimed invention. An adequate written description of the invention may be shown by any description of sufficient, relevant, identifying characteristics so long as a person skilled in the art would recognize that the inventor had possession of the claimed invention.
According to MPEP 2163.II.A.3.(a).ii), “Satisfactory 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.’"
In the instant case, the claims broadly encompass methods for treating organisms infected by infectious agents by identifying essential genes and permanently inactivating such genes using CRISPR-based nucleic acid targeting systems. However, the specification demonstrates possession only of a single, highly specific example involving a CRISPR knockout of the fabI gene in a non-pathogenic Escherichia coli K-12 strain, performed in vitro, grown on LB agar/medium, explicitly “not in a human organism”. The example explains that fabI in non‑pathogenic K‑12 E. coli is targeted because it is understood to serve an important function of synthesizing cell wall lipids and that when fabI is knocked out the E. coli will die. The disclosure of this single non‑pathogenic K‑12 E. coli laboratory knockout is not commensurate in scope with the full breadth of the claimed invention
The specification does not describe, nor provide representative species or structural features sufficient to support, the broad genus of claimed methods encompassing: different infectious agents (including diverse bacteria, viruses, or other pathogens), different essential genes, different guide RNA designs, different nucleases, different delivery mechanisms, or treatment in a living organism. Rather, applicants describe a research workflow for identifying targets and designing CRISPR reagents, which constitutes a plan for future experimentation rather than a description demonstrating possession of the full scope of the claimed invention.
Claim 2 encompasses the genus of methods recited in claim 1, wherein the nuclease is Cas9. Claim 3 encompasses the genus of methods of claim 1, wherein the infectious agent is limited to MRSA, E. coli, S. aureus, S. eneterica and S. pyogenes. Claim 4 encompasses the genus of methods recited in claim 1, wherein the function materially contributes to cell wall synthesis, cell membrane synthesis, metabolism, reproduction, and cell duplication. And is further limited in claim 5 to synthesis of cell wall lipids. However, these additional limitations do not remedy the lack of written description as a whole, identified above. The dependent claims merely narrow aspects of the method.
Accordingly, the specification fails to reasonably convey possession of the claimed invention commensurate in scope with claims 1-5, and the claims are rejected for lack of written description.
Claims 1-5 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method of treating a non-pathogenic E. coli by CRISPR-mediated gene knockout of FabI, does not reasonably provide enablement for the claimed genus of methods encompassing treating of any organism for any disease caused by any infectious agent, by administering a CRISPR RNP complex that affects any protein necessary for survival or performance of any function required by the infectious agent. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
The specification fails to enable the claim (or the full scope of the claim) if a person of ordinary skill in the art would be faced with an undue burden of experimentation when trying to implement the invention based on the disclosure. In re Wands (858 F.2d 731 at 737, 8 USPQ2d 1400 at 1404 (Fed. Cir. 1988)) sets forth a non-exclusive list of factors by which this burden of experimentation may be judged to be due or undue; factors that are germane to the instant case include the breadth of the claims, nature of the invention, the amount of direction provided by the inventor, the existence of working examples, the state of the prior art, and quantity of experimentation required.
Breadth of the Claims and Nature of the Invention
Claim 1 encompasses methods for treating any organism (e.g., human, animal) infected with any “infectious agent,” which on its face includes bacteria, viruses, fungi, and parasites, by determining “essential” proteins and genes, designing gRNAs and RNP complexes, and administering those RNP complexes to the organism. Claim 2 specifies wherein the nuclease is Cas9. Claims 3 and 4-5 cover at least five different bacterial pathogens and multiple essential cellular functions.
This scope includes, without limitation, multiple classes of infectious agents, multiple essential genes, multiple CRISPR nucleases in claims 1 and 3-5 and multiple guide RNAs, and administration to an unknown organism. However, the specification provides only a single example directed to an in vitro CRISPR knockout of the fabI gene in a non-pathogenic E. coli K-12 strain. No working examples demonstrate treatment of an organism, delivery of CRISPR complexes to infectious agents in vivo, or therapeutic efficacy.
Accordingly, the breadth of the claims far exceeds the narrow disclosure.
State of the Prior Art and Level of Predictability
While CRISPR technology for gene editing is known in the art, the application of CRISPR-based ribonucleoprotein complexes as therapeutic agents for selectively killing infectious agents within a treated organism remains highly unpredictable, particularly with respect to target selection across diverse pathogens, delivery to infectious agents within a host, and achieving therapeutic efficacy without off-target effects. The unpredictability of biological systems weighs against enablement across the full scope of the claims.
Amount of Direction and Presence of Working Examples
The only detailed working example described on the provided page is a CRISPR knockout of the fabI gene in non-pathogenic K-12 E. coli on LB agar/medium, explicitly not in a human organism and without any in vivo delivery into an infected host. The example explicitly notes that “the process would be altered for testing and application in humans,” but does not provide sufficient teaching regarding how to modify the in vitro bacterial culture procedure into a safe and effective therapeutic method in an infected organism (e.g., dosage, route of administration, formulation, targeting, immune effects, off‑target considerations). Therefore, the specification provides no guidance regarding how CRISPR ribonucleoprotein complexes are delivered to infectious agents within an organism, how treatment efficacy is assessed in vivo, or how safety concerns are addressed.
Undue Experimentation
Absent additional guidance, a person of ordinary skill in the art would be required to engage in extensive experimentation for each pathogen and each essential function, including genome‑wide identification of essential genes, design and validation of gRNAs and PAM sites, construction and testing of RNP complexes, and optimization of in vivo delivery and dosing in infected organisms. The specification, limited to a single non‑pathogenic E. coli laboratory example without therapeutic in vivo data, does not provide sufficient guidance to reduce this experimentation to routine optimization.
In view of the breadth of the claims relative to the narrow disclosure, the limited number of working examples, the complexity and relative unpredictability of in vivo CRISPR‑based antimicrobial therapy, and the amount of experimentation required to extend the disclosed E. coli example to the full range of infectious agents and treatment scenarios encompassed by the claims, one of ordinary skill in the art would not be able to practice the claimed invention without undue experimentation.
Thus, claims 1-5 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, for lack of enablement.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-4 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Citorik et al. (Sequence-specific antimicrobials using efficiently delivered RNA-guided nucleases, Nat Biotechnol. 2014 November ; 32(11): 1141–1145, cited in PTO-892).
Pursuant to MPEP 2111.02 II: The claim preamble must be read in the context of the entire claim. The determination of whether preamble recitations are structural limitations or mere statements of purpose or use "can be resolved only on review of the entirety of the [record] to gain an understanding of what the inventors actually invented and intended to encompass by the claim" as drafted without importing "'extraneous' limitations from the specification." Corning Glass Works, 868 F.2d at 1257, 9 USPQ2d at 1966. If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction. Therefore, “treating an organism for a disease caused by an infectious agent in the organism” recited in claim 1 will be interpreted as an intended use, and as such, thus not given patentable weight.
Furthermore, claim 1 recites multiple “determining” steps, including “determining at least one protein necessary for performance of a function the infectious agent requires for survival” and determining corresponding gene, target sequence, PAM site, and guide RNA sequence. These steps recite mental processes involving selection or identification of information and do not require any affirmative physical action beyond ordinary reasoning by a person of ordinary skill in the art. Once a target gene or protein is selected for targeting, the remaining determinations necessarily and inherently follow, as identification of target sequences, PAM sites, and corresponding guide RNA sequences is an inherent aspect of designing an RNA-guided nuclease system. Accordingly, these “determining” steps are not given patentable weight.
As such, when the preamble and the non-limiting “determining” steps are not given patentable weight, claim 1 is directed to preparing a ribonucleoprotein (RNP) complex including a gRNA sequence and a nuclease; and administering the RNP complex to an organism.
Regarding claims 1-3, Citorik et al. discloses preparing RNA-guided nuclease (RGN) systems comprising Cas9 nuclease complexed with RNA components, including crRNA and tracrRNA, which guide the nuclease to a sequence specific DNA target in bacteria (Abstract and pg. 2, 2nd para). Citorik et al. teaches preparing such RGN systems by constructing plasmid (phagemid) vectors encoding Cas9 and crRNA spacer sequences and packaging those constructs into bacteriophage particles for delivery (pg. 7, bottom para – pg. 9, paras 1 and 2). Citorik et al. also discloses administering the prepared RGNs to bacterial cells by delivering phage packaged ΦRGNs to E. coli, resulting in sequence specific DNA cleavage and loss of viability. More specifically, Citorik et al. discloses ΦRGNgyrAD87G targeting the chromosomal gyrAD87G gene in quinolone-resistant E. coli, wherein treatment resulted in cytotoxicity only in cells harboring the gyrAD87G mutation (pg. 4, 2nd para and Fig. 1).
Regarding claim 4, as described above, Citorik et al. teaches targeting the gyrA gene, which disrupts DNA gyrase activity – a core metabolic function required for DNA replication and cell viability.
Thus, claims 1-4 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Citorik et al.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
Claims 1-4 are rejected under 35 U.S.C. 103 as being unpatentable over Citorik et al. (Sequence-specific antimicrobials using efficiently delivered RNA-guided nucleases, Nat Biotechnol. 2014 November ; 32(11): 1141–1145, cited in PTO-892).
As indicated above, the preamble of claim 1, reciting “treating an organism for a disease caused by an infectious agent in the organism”, is interpreted as stating an intended use, and as such, thus not given patentable weight. Claim 1 further recited multiple “determining” steps, as described above, and are interpreted as non-limiting mental processes and/or inherent design considerations that necessarily follow from selection of a target. However, even if the preamble of claim 1 were given patentable weight, treating an organism for a disease caused by an infectious agent, as recited, would have been obvious to a person of ordinary skill in the art in view of the teachings of Citorik et al., as discussed below. Further, even if the “determining” steps recited in claim 1 were considered to impose limitations, such steps would have been obvious and/or inherent, as detailed below.
Regarding claims 1-3, Citorik et al. teaches the use of CRISPR-Cas technology to “create antimicrobials whose spectrum of activity is chosen by design”, wherein RNA-guided nucleases (RGNs) “targeting specific DNA sequences are delivered efficiently to microbial populations using bacteriophage or bacteria carrying plasmids transmissible by conjugation”. Citorik et al. further teaches that the DNA targets of RGNs can be undesirable genes or polymorphisms, including “antibiotic resistance and virulence determinants in carbapenem-resistant Enterobacteriaceae and enterohemorrhagic Escherichia coli” (Abstract). Citorik et al. also illustrates RGN constructs delivered by bacteriophage particles that exhibit efficient and specific antimicrobial effects against strains harboring plasmid or chromosomal target sequences in Fig. 1a-c (pg. 15), characterization of RGN mediated killing of antibiotic resistant bacteria in Fig. 2a-d (pg. 16) and sequence specific toxicity of RGN particles against E. coli in vitro and in vivo in Fig. 3a-b (pg. 17). More specifically, Citorik et al. teaches targeting specific genes whose disruptions results in loss of viability (i.e., required for survival), such as gyrA in quinolone-resistant E. coli harboring the chromosomal gyrAD87G mutation (pg. 4, para 2). Because the gyrA D87G mutation confers quinolone resistance, disruption of this gene would also be understood to remove the genetic basis for such resistance, thereby rendering surviving cells susceptible to antibiotic therapy and further compromising bacterial survival. While Citorik et al. does not label a “determining” step for identifying/determining these “necessary” genes and proteins in the infectious agent, this step is necessarily performed by disclosing the identification and selection of specific targets and corresponding DNA sequences in order to design the RGNs that are constructed and experimentally validated. Citorik et al. discloses selection of specific DNA target sequences for RGN cleavage through the design of crRNA spacer sequences complementary to the target loci. It is noted that crRNA here corresponds to a guide RNA, as understood by persons of ordinary skill in the art and required by the instant claim. It is further noted that the “RNA-guided nuclease” as taught by Citorik et al. comprises a Cas9 nuclease in complex with RNA components (crRNA and tracrRNA) that guide the nuclease to a specific DNA target, and therefore corresponds to a “ribonucleoprotein complex” as claimed (see also Fig. 1a). Citorik et al. expressly teaches that “with the aid of a transactivating small RNA (tracrRNA), crRNAs enable the Cas9 endonuclease to introduce double-stranded breaks in target DNA sequences. Through simple modifications of spacers in the CRISPR locus, an RGN can direct cleavage of almost any DNA sequence…”(pg. 2, para 2). Regarding the at least one protospacer adjacent motif (PAM) site recited in claim 1, Citorik et al. further teaches that Cas9 mediated cleavage requires “a requisite NGG motif immediately 3′ of the target sequence” (pg. 2, para 2), such that identification of a target sequence necessarily includes identification of an adjacent PAM site capable of being recognized by the nuclease.
Regarding claim 4, as described above, Citorik et al. teaches targeting the chromosomal gyrA gene in quinolone-resistant E. coli harboring the gyrA D87G mutation, resulting in loss of bacterial viability. A person of ordinary skill in the art would recognize that disruption of gyrA eliminates DNA gyrase activity, a core metabolic function required for DNA replication, transcription, and cell division.
An invention would have been obvious to a person of ordinary skill in the art if some teaching in the prior art would have led that person to arrive at the claimed invention. Before the effective filing date of the claimed invention it would have been obvious to a person of ordinary skill in the art to treat an organism inflicted with a disease caused by an infectious agent, using the RNA-guided nuclease (RGN) system as taught by Citorik et al. Citorik et al. expressly teaches the use of CRISPR-Cas based RNA-guided nucleases to selectively target and disrupt specific DNA sequences within pathogenic bacteria, including genes associated with core metabolic function, antibiotic resistance and virulence, in order to induce cell death, plasmid loss, or loss of viability. A person of ordinary skill in the art would have recognized that administering such RGNs to an organism afflicted with a disease caused by an infectious agent would predictably treat the disease by selectively eliminating or disabling the infectious agent through sequence-specific DNA cleavage. Given Citorik et al.’s successful demonstration that RGNs may be rationally designed by selecting target genes essential for survival or pathogenicity, identifying corresponding target DNA sequences and adjacent PAM sites, and constructing crRNA spacer sequences to guide Cas9-mediated cleavage, there is a reasonable expectation of success in applying the disclosed antimicrobial CRISPR-Cas systems for therapeutic treatment. Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention.
Thus, claims 1-4 are rejected under 35 U.S.C. 103 as being unpatentable over Citorik et al.
Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Citorik et al., as applied to claims 1 and 4 above, and further in view of Bergler et al. (The Enoyl-[Acyl-Carrier-Protein] Reductase (FabI) of Escherichia coli, which Catalyzes a Key Regulatory Step in Fatty Acid Biosynthesis, Accepts NADH and NADPH as Cofactors and is Inhibited by Palmitoyl-CoA. 1994. European Journal of Biochemistry, 242: 689-694, cited in PTO-892).
The teachings of Citorik et al., as they apply to claims 1 and 4, have already been discussed. Briefly, Citorik et al. discloses the use of CRISPR-Cas technology to create sequence specific antimicrobials, wherein RNA guided nucleases comprising a Cas9 nuclease and RNA components are designed to target specific DNA sequences in bacteria, resulting in loss of viability of the targeted bacterial cells. Citorik et al. specifically demonstrate such sequence specific killing in bacteria, including antibiotic resistant E. coli, by directing RGNs to defined chromosomal or plasmid encoded genes whose disruption compromises bacterial survival. However, Citorik et al. does not expressly disclose targeting genes or proteins that are specifically responsible for the synthesis of cell wall lipids.
Regarding claim 5, Bergler et al. discloses enoyl-acyl-carrier-protein reductase (FabI) of E. coli, which catalyzes a key regulatory step in fatty acid biosynthesis. Bergler et al. teaches that FabI activity is central to endogenous fatty acid production and that mutations in FabI result in reduced enzymatic activity and temperature sensitive growth, demonstrating that FabI materially contributes to lipid biosynthesis required for normal bacteria growth (Abstract).
An invention would have been obvious to a person of ordinary skill in the art if some teaching in the prior art would have led that person to arrive at the claimed invention. Before the effective filing date of the claimed invention, the teachings of Citorik et al., that RNA-guided nucleases can selectively target and disrupt specific DNA sequences within pathogenic bacteria in order to induce cell death, plasmid loss, or loss of viability, and the teachings of Bergler et al., that FabI of E. coli catalyzes a key regulatory step in fatty acid biosynthesis, would have led a person of ordinary skill in the art to design the RNA guided nuclease disclosed by Citorik et al. to target FabI in E. coli. A person of ordinary skill in the art would have been motivated to make such a modification because Bergler et al. discloses that mutations in the fabI gene affect enoyl-acyl-carrier-protein reductase activity and alter fatty acid biosynthesis in E. coli, which interferes with cell wall lipid synthesis and normal bacterial growth. Therefore, it would be obvious for a person of ordinary skill in the art, to substitute the intended target gyrA for FabI instead, and expect predictable results (see MPEP 2144.06, “Substituting equivalents known for the same purpose”). There is a reasonable expectation of success, given Citorik et al.’s successful demonstration of sequence specific targeting of bacterial genes, such as gyrA, using RNA-guided nucleases in E. coli. Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention.
Thus, claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Citorik et al., as applied to claims 1 and 4 above, and further in view of Bergler et al.
Conclusion
No claim is in condition for allowance.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NAGHMEH NINA MOAZZAMI whose telephone number is (703)756-4770. The examiner can normally be reached Monday-Friday, 9:00-5:00.
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/NAGHMEH NINA MOAZZAMI/Examiner, Art Unit 1652
/RICHARD G HUTSON/Primary Examiner, Art Unit 1652