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 without traverse of Group I, claims 1-5 and 9-17 and species: Cas9, VirD2, and SEQ ID NO: 17 in the reply filed on 2/26/2026 is acknowledged. The election of species requirement between Cas enzymes, relaxases, and SEQ ID NOS 16-18 is withdrawn and the species are rejoined.
Claim Status
Claims 20-24 are withdrawn from consideration as being directed to a non-elected invention.
An action on the merits of claims 1-5 and 9-17 is set forth herein.
Information Disclosure Statement
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.
Specification
The disclosure is objected to because the Brief description of the figures does not include a description of figure 6. Appropriate correction is required, however care should be taken not to introduce new matter into the specification.
Claim Rejections - 35 USC § 112
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.
Claims 1-5 and 9-15 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.
Relevant to the lack of particular structural limitations in the rejected claims drawn to CRISPR Cas enzyme-relaxase fusion proteins, MPEP 2163 states:
The claimed invention as a whole may not be adequately described if the claims require an essential or critical feature which is not adequately described in the specification and which is not conventional in the art or known to one of ordinary skill in the art.
Additionally, at 2163IIA3(a), the MPEP states:
“…describing a composition by its function alone typically will not suffice to sufficiently describe the composition. See Eli Lilly, 119 F.3 at 1568, 43 USPQ2d at 1406 (Holding that description of a gene’s function will not enable claims to the gene “because it is only an indication of what the gene does, rather than what it is.”); see also Fiers, 984 F.2d at 1169-71, 25 USPQ2d at 1605-06 (discussing Amgen Inc. v. Chugai Pharm. Co., 927 F.2d 1200, 18 USPQ2d 1016 (Fed. Cir. 1991)). An adequate written description of a chemical invention also requires a precise definition, such as by structure, formula, chemical name, or physical properties, and not merely a wish or plan for obtaining the chemical invention claimed. See, e.g., Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 927, 69 USPQ2d 1886, 1894-95 (Fed. Cir. 2004) (The patent at issue claimed a method of selectively inhibiting PGHS-2 activity by administering a non-steroidal compound that selectively inhibits activity of the PGHS-2 gene product, however the patent did not disclose any compounds that can be used in the claimed methods. While there was a description of assays for screening compounds to identify those that inhibit the expression or activity of the PGHS-2 gene product, there was no disclosure of which peptides, polynucleotides, and small organic molecules selectively inhibit PGHS-2. The court held that “[w]ithout such disclosure, the claimed methods cannot be said to have been described.”).
The claims are broadly drawn to methods of detecting target nucleic acids using a fusion protein comprising any CRISPR cas enzyme-relaxase.
In the case of the instant claims, the functionality of identifying CRISPR cas enzyme relaxase fusion proteins which are capable of detecting target nucleic acids is a critical feature of the claimed methods.
The specification teaches constructing fusion proteins comprising Cas9 and VirD2 relaxase encoded by a nucleic acid selected from the group consisting of SEQ ID NOS 16, 17, and 18. However, the specification does not teach any other Cas9 VirD2 fusion proteins, let alone any other genus of possible CRISPR Cas enzymes fused to any other relaxase.
While the skilled artisan may be capable of making fusion proteins comprising a Cas enzyme and a relaxase, possession may not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features. See University of Rochester, 358 F.3d at 927, 69 USPQ2d at 1895.
The claims encompass a genus of structurally undefined fusion proteins with a specific functionality. The specification only teaches a Cas9-VirD2 fusion protein encoded by SEQ ID NO: 16, 17, or 18. However, the variability in obtaining Cas fusion proteins with desired functionality is acknowledged by the prior art (see eg Ribeiro et al; International Journal of Genomics, doi.org/10.1155/2018/1652567, pages 1-12; 2018). The simply designation of a general formula “CAS-relaxase” or “relaxase-CAS” does not provide a description of the structure of fusion proteins with the desired function. This generic formula does not provide a description of the protein sequences which would be capable of functioning as claimed vs those that do not. The description of 3 species, all directed to only a single CAS enzyme (Cas9) and a single relaxase (VirD2) is not representative of the broad genus claimed given the art acknowledged limitations in designing fusion proteins comprising Cas9 with a particular functionality (see Ribeiro).
For claims drawn to a genus, the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species. A “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (Claims directed to a functionally defined genus of antibodies were not supported by a disclosure that “only describe[d] one type of structurally similar antibodies” that “are not representative of the full variety or scope of the genus.”). The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure “indicates that the patentee has invented species sufficient to constitute the gen[us].” See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615. Further, University of California v. Eli Lilly and Co., 43 USPQ2d 1398, 1404, 1405 held that:
To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that “the inventor invented the claimed invention.” Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (1997); In re Gosteli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (“ [T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed.”). Thus, an applicant complies with the written description requirement “by describing the invention, with all its claimed limitations, not that which makes it obvious,” and by using “such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention.” Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966.
Thus considering the breadth of the fusion proteins required by the claimed methods, their specific required functionalities, and the teachings of the instant specification, it is the conclusion that the specification does not provide an adequate written description of the broadly claimed subject matter.
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.
Claims 1-5 and 9-17 are rejected 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 regards as the invention.
The use of the parenthesis in claim 1 is confusing because it is not clear if the term within is part of the claimed invention or not. It is further unclear if the term “probe” refers to the nucleic acid sequence or to the relaxase.
The claims contain numerous grammar errors. For example, the use of the plural term “relaxases” in claim 2 is confusing because it is not clear if more than one relaxase is being referred to or not. This is not an exhaustive list. ALL claims should be thoroughly reviewed for singular/plural agreement, mixed tense (using both past and present tense in the claims), typographical errors, lack of proper articles (eg: a, the), consistency in terms (eg: claim 11 uses both terms bind and binding for the same action) etc. Appropriate correction is required for all claims.
The recitation of “the spacer” in claim 4 lacks sufficient antecedent basis and renders the claim indefinite because it is not clear what “spacer” is being referred to. Appropriate correction is required.
Claim 9 is narrative in nature. The multiple recitations of comprising are confusing such that the actual steps required by the claim are unclear. For example, it appears that the claim requires forming a reporter complex twice. Appropriate correction is required.
The term “analyte of interest” in claim 10 is confusing because it is not clear what its function is or where it is used in the method of claim 1. Is the “analyte of interest” the same as the “target nucleic acid”? Is it being detected or used in the method? Appropriate correction is required.
Claim 11 is confusing because it is not clear which limitations are directed to method steps and which limitations are meant to further limit a structure or component in the method. Appropriate correction is required.
The term “running buffer” in claim 11 is confusing because it is not clear what the function of the “running buffer” is or what it’s components are. Additionally, the list of reagents in the claim lack a conjunction (and, or) at the end of the list such that it isn’t clear if the buffer comprises ALL of the components or only one of them. Is this list a Markush group of alternatively usable species? Appropriate correction is required.
The use of the term “preferably” in claim 13 is indefinite because it is not clear if this is a limitation or not. A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. Appropriate correction is required.
Claim 14 is indefinite because the use of the term “about” renders the metes and bounds of the component concentrations unclear. Claim 14 depends from claim 11, which provides ranges for the components, however it is not clear if the term “about” in claim 14 is broader than the ranges listed in claim 11. Additionally, the term “about” is misspelled. Appropriate correction is required.
In claim 15 it is not clear if the term “stetavisin” is misspelled. Additionally the structure of “anti anti FAM antibodies” is not clear. Appropriate correction is required.
The reference to “one line” or “two lines” in claim 15 lack sufficient antecedent basis. It is not clear what these lines are, what their purpose is, which step in the method produces them, or where they are located. Appropriate correction is required.
Although the wording of claims 16 and 17 are slightly different, they appear to be identical in scope. It is not clear what the difference in scope is between the two claims. Appropriate correction or explanation is required.
Allowable subject matter
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Ali (Ali et al; Communications Biology, doi.org/10.1038/s42003-020-0768-9; pages 1-13) teaches a fusion protein comprising Cas9 endonuclease and VirD2 relaxase for genome editing in rice. However, Ali does not teach a method of detecting a target nucleic acid in a sample comprising:
(i) amplifying the target nucleic acid to generate an amplified target nucleic acid comprising a first label, and
(ii) contacting the target nucleic acid with a) a chimeric fusion protein comprising Cas9 and VirD2, b) an sgRNA specific for the target nucleic acid molecule, and c) a nucleic acid probe sequence comprising a second label, where in the probe sequence is recognized by the relaxase.
The following claim is free of the prior art and allowable:
A method of detecting target nucleic acids in a sample comprising:
(i) amplifying the target nucleic acids to generate amplified target nucleic acids comprising a first label, and
(ii) contacting the amplified target nucleic acids with a) a chimeric fusion protein comprising Cas9 and VirD2 encoded by the nucleic acid sequence of SEQ ID NO 16, 17, or 18, b) an sgRNA specific for the target nucleic acid molecule, and c) a nucleic acid probe sequence comprising a second label, wherein the probe sequence is recognized by the relaxase.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to examiner Jehanne Sitton whose telephone number is (571) 272-0752. The examiner is a hoteling examiner and can normally be reached Mondays-Fridays from 8:00 AM to 2:00 PM Eastern Time Zone.
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, Winston Shen, can be reached on (571) 272-3157. The fax phone number for organization where this application or proceeding is assigned is (571) 273-8300.
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/JEHANNE S SITTON/Primary Examiner, Art Unit 1682
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