Detailed Office 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 .
Status of the Claims
Acknowledgement is hereby made of receipt and entry of the communication filed 13 October, 2025. Claims 1-20 are pending in the instant application. Applicant’s election of Group VIII (claims 16-20) without traverse for examination on the merits is noted. Claims 1-15 have been withdrawn from further consideration by the Examiner, pursuant to 37 C.F.R. § 1.142(b), as being drawn to a non-elected invention.
37 C.F.R. § 1.98
The information disclosure statement filed 03 July, 2024, has have been placed in the application file and the information referred to therein has been considered. Applicant is reminded that the listing of references in the specification is not a proper information disclosure statement. 37 C.F.R. § 1.98(b) requires a list of all patents, publications, applications, or other information submitted for consideration by the Office, and M.P.E.P. § 609.04(a), subsection I. 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.
37 C.F.R. § 1.84
The drawings filed 03 October, 2022, have been reviewed and are acceptable.
35 U.S.C. § 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 19 and 20 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. Two separate requirements are set forth under this statute: (1) the claims must set forth the subject matter that applicants regard as their invention; and (2) the claims must particularly point out and distinctly define the metes and bounds of the subject matter that will be protected by the patent grant.
Claim 19 references a method and assay that are comprised by a container. This recitation is vague and indefinite since it is not readily manifest how a method/assay are contained within a container. Appropriate correction is required.
Claim 20 references “the viral” RNA. However, there is insufficient antecedent basis for this limitation in the claim. Appropriate correction is required.
35 U.S.C. § 112(a)
The following is a quotation 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.
Written Description
Claims 16-20 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. Amgen, Inc. v. Sanofi, 872 F.3d 1367, 124 U.S.P.Q.2d 1354 (Fed. Cir. 2017). AbbVie Deutschland GmbH & Co. v. Janssen Biotech, Inc., 759 F.3d 1285, 111 U.S.P.Q.2d 1780 (Fed. Cir. 2014). Univ. of Rochester v. G.D. Searle & Co., Inc., 358 F.3d 916, 920, 69 U.S.P.Q.2d 1886, (Fed. Cir. 2004). Enzo Biochem, Inc. v. Gen-Probe, Inc., 296 F.3d 1316, 63 U.S.P.Q.2d 1609, (Fed. Cir. 2002). Regents of the University of California v. Eli Lilly & Co., 119 F.3d 1559, 43 U.S.P.Q.2d 1398, (Fed. Cir. 1997). Fiers v. Revel Co., 984 F.2d 1164, 25 U.S.P.Q.2d 1601, (Fed. Cir. 1993). Amgen, Inc. v. Chugai Pharmaceutical Co., 927 F.2d 1200, 18 U.S.P.Q.2d 1016, (Fed. Cir. 1991). In re Rasmussen, 650 F.2d 1212, 211 U.S.P.Q. 323 (C.C.P.A. 1981). In re Wertheim, 541 F.2d 257, 191 U.S.P.Q. 90 (C.C.P.A. 1976).
The crux of the statutory requirement governing written description is whether one skilled in the art, familiar with the practice of the art at the time of the filing date, could reasonably have found the later claimed invention in the specification as filed. In re Kaslow, 707 F.2d 1366, 1375, 217 U.S.P.Q. 1089, 1096 (Fed. Cir. 1983). In re Wilder, 736 F.2d 1516, 1520 222 U.S.P.Q. 349, 372 (Fed. Cir. 1984, cert. denied, 469 U.S. 1209 (1985). Texas Instruments, Inc. v. International Trade Comm’n, 871 F.2d 1054, 1063, 10 U.S.P.Q.2d 1257, 1263 (Fed. Cir. 1989). Moreover, the courts have stated that the evaluation of written description is highly fact-specific, and that broadly articulated rules are inappropriate. In re Wertheim, 541 F.2d 257, 263, 191 U.S.P.Q. 90, 97 (C.C.P.A. 1976). In re Driscoll, 562 F.2d 1245, 1250, 195 U.S.P.Q. 434, 438 (C.C.P.A. 1977). It is also important to remember that the true issue in question is not whether the specification enables one of ordinary skill in the art to make the later claimed invention, but whether or not the disclosure is sufficiently clear that those skilled in the art will conclude that the applicant made the invention having the specific claim limitations. Martin v. Mayer, 823 F2d 500, 505, 3 U.S.P.Q.2d 1333, 1337 (Fed. Cir. 1987).
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 has possession of the claimed invention. See, e.g., Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 U.S.P.Q.2d at 1116. An applicant shows possession of the claimed invention by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention. Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 U.S.P.Q.2d 1961, 1966 (Fed. Cir. 1997). The claimed invention as a whole may not be adequately described where an invention is described solely in terms of a method of its making coupled with its function and there is no described or art-recognized correlation or relationship between the structure of the invention and its function. A biomolecule sequence described only by a functional characteristic, without any known or disclosed correlation between that function and the structure of the sequence, normally is not a sufficient identifying characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence. A lack of adequate written description issue also arises if the knowledge and level of skill in the art would not permit one skilled in the art to immediately envisage the product claimed from the disclosed process. Fujikawa v. Wattanasin, 93 F.3d 1559, 1571, 39 U.S.P.Q.2d 1895, 1905 (Fed. Cir. 1996).
Determination of adequate written description requires the Examiner to read and analyze the specification for compliance with 35 U.S.C. § 112(a). In particular, each claim should be analyzed to determine its broadest reasonable interpretation consistent with written description. Each claim should be evaluated to determine if sufficient structures, acts, or functions are recited to make clear the scope and meaning of the claim, including the weight to be given the preamble. The entire application should be reviewed including the specific embodiments, figures, and sequence listings, to understand how applicant provides support for the various features of the claimed invention. The analysis of whether the specification complies with the written description requirement calls for the examiner to compare the scope of the claim with the scope of the description to determine whether applicant has demonstrated that the inventor was in possession of the claimed invention. Such a review is conducted from the standpoint of one of ordinary skill in the art at the time the application was filed (see, e.g., Wang Labs., Inc. v. Toshiba Corp., 993 F.2d 858, 865, 26 USPQ2d 1767, 1774 (Fed. Cir. 1993)) and should include a determination of the field of the invention and the level of skill and knowledge in the art. Finally, the Examiner should determine whether there is sufficient written description to inform a skilled artisan that the inventor was in possession of the claimed invention as a whole at the time of filing.
The claims are directed toward a method comprising adding an isolated or recombinantly expressed protein comprising the sequence of SEQ ID NO: 1, or an amino acid sequence that is at least 90% identical to the sequence of SEQ ID NO: 1, across a contiguous segment of SEQ ID NO:1 that is from 10-232 amino acids in length, to an assay, the assay comprising RNA from a biological sample, a Cas13, and a guide RNA targeted to an RNA polynucleotide that may be in the biological sample, and determining whether or not the Cas13 cleaves a reporter RNA that is added to the sample before or after addition of the protein.
The claims are directed toward a large genus of AcrVIA1 variant polypeptides. AcrVIA1 (SEQ ID NO.: 1; 232 aa) has the following amino acid sequence: MIYYIKDLKV KGKIFENLMN KEAVEGLITF LKKAEFEIYS RENYSKYNKW FEMWKSPTSS LVFWKNYSFR CHLLFVIEKD GECLGIPASV FESVLQIYLA DPFAPDTKEL FVEVCNLYEC LADVTVVEHF EAEESAWHKL THNETEVSKR VYSKDDDELL KYIPEFLDTI ATNKKSQKYN QIQGKIQEIN KEIATLYESS EDYIFTEYVS NLYRESAKLE QHSKQILKEE LN. However, the claims encompass upwards of 10% amino acid sequence variation at any stretch that is 10-232 amino acids in length. Just considering amino acid substitutions, this would encompass upwards of ~3 x 1060 variant amino sequences.1 The claims also encompass insertions and deletions anywhere within the anti-CRISPR protein.
The disclosure fails to provide adequate guidance with respect to the molecular determinants modulating AcrVIA1-Cas13 binding interactions. Furthermore, the art doesn’t appear to shed any illumination on these considerations either (Lin et al., 2020; Meeske et al., 2020). Accordingly, it is not readily manifest which portions of the anti-CRISPR protein can tolerate amino acid insertions, deletions, or replacements. Moreover, perusal of the disclosure fails to provide any support for the claimed genus of AcrVIA1 variants. There was no evidence demonstrating that Applicant generated a reasonable number of AcrVIA1 variants and subjected them to further characterization. Accordingly, the skilled artisan would reasonably conclude that Applicant was not in possession of a representative number of AcrVIA1 variants.
When all the aforementioned factors are considered in toto, the skilled artisan would reasonably conclude that Applicant was not in possession of a sufficient number of anti-CRISPR AcrVIA1 variants to support the desired claim breadth.
Scope of Enablement
Claims 16-20 are rejected under 35 U.S.C. § 112(a), because the specification does not reasonably enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims. The claims are directed toward a method comprising adding an isolated or recombinantly expressed protein comprising the sequence of SEQ ID NO: 1, or an amino acid sequence that is at least 90% identical to the sequence of SEQ ID NO: 1, across a contiguous segment of SEQ ID NO:1 that is from 10-232 amino acids in length, to an assay, the assay comprising RNA from a biological sample, a Cas13, and a guide RNA targeted to an RNA polynucleotide that may be in the biological sample, and determining whether or not the Cas13 cleaves a reporter RNA that is added to the sample before or after addition of the protein.
The legal considerations that govern enablement determinations pertaining to undue experimentation have been clearly set forth. Enzo Biochem, Inc., 52 U.S.P.Q.2d 1129 (C.A.F.C. 1999). In re Wands, 8 U.S.P.Q.2d 1400 (C.A.F.C. 1988). Ex parte Forman 230 U.S.P.Q. 546 (PTO Bd. Pat. App. Int., 1986). The courts concluded that several factual inquiries should be considered when making such assessments including the quantity of experimentation necessary, the amount of direction or guidance presented, the presence or absence of working examples, the nature of the invention, the state of the prior art, the relative skill of those in that art, the predictability or unpredictability of the art and the breadth of the claims. In re Rainer, 52 C.C.P.A. 1593, 347 F.2d 574, 146 U.S.P.Q. 218 (1965).
The disclosure fails to provide adequate guidance pertaining to a number of these considerations as follows:
1) The claim breadth encompasses a large genus of AcrVIA1 variants.
AcrVIA1 (SEQ ID NO.: 1; 232 aa) has the following amino acid sequence: MIYYIKDLKV KGKIFENLMN KEAVEGLITF LKKAEFEIYS RENYSKYNKW FEMWKSPTSS LVFWKNYSFR CHLLFVIEKD GECLGIPASV FESVLQIYLA DPFAPDTKEL FVEVCNLYEC LADVTVVEHF EAEESAWHKL THNETEVSKR VYSKDDDELL KYIPEFLDTI ATNKKSQKYN QIQGKIQEIN KEIATLYESS EDYIFTEYVS NLYRESAKLE QHSKQILKEE LN. However, the claims encompass upwards of 10% amino acid sequence variation at any stretch that is 10-232 amino acids in length. Just considering amino acid substitutions, this would encompass upwards of ~3 x 1060 variant amino sequences.2 The claims also encompass insertions and deletions anywhere within the anti-CRISPR protein.
2) The disclosure fails to provide adequate guidance pertaining to the molecular determinants modulating AcrVIA1 binding to Cas13a and its guide RNA (gRNA). While some critical contact residues were identified in AcrVIA1 that appear to interact with the crRNA-exposed face, nevertheless, mutants involving these contact residues, or other regions throughout AcrVIA1 were not provided. Thus, the Examiner cannot reasonably predict how any given amino acid substitution, insertion, or deletion will impact AcrVIA1:Cas13a/gRNA binding interactions.
3) The disclosure only provides a single working embodiment involving the AcrVIA1 of SEQ ID NO.: 1. No other variants were generated, expressed, and characterized for anti-Cas13a activity. Thus, the skilled artisan has been extended an invitation to further undue experimentation to identify suitable AcrVIA1 mutants or variants.
4) The prior art also fails to provide any further illumination with respect to the molecular determinants modulating the anti-CRISPR activity of AcrVIA1 (Lin et al., 2020; Meeske et al., 2020).
Accordingly, when all the aforementioned factors are considered in toto, the skilled artisan would reasonably conclude that undue experimentation would be required to practice the claimed invention in a manner commensurate in scope with the claims.
Correspondence
Any inquiry concerning this communication should be directed to Jeffrey S. Parkin, Ph.D., whose telephone number is (571) 272-0908. The Examiner can normally be reached Monday through Friday from 10:00 AM to 6:00 PM. A message may be left on the Examiner's voice mail service. 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 are unsuccessful, the Examiner's supervisor, Michael Allen, Ph.D., can be reached at (571) 270-3497. Direct general status inquiries to the Technology Center 1600 receptionist at (571) 272-1600.
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Respectfully,
/JEFFREY S PARKIN/Primary Examiner, Art Unit 1671 10 January, 2026
1 These calculations were performed as follows: TV=(NY)(X!)/(Y!)((X-Y-1)!), wherein, TV=the total number of variant sequences, N=the number of amino acids or nucleotides that can be substituted (i.e., if any of the 20 naturally occurring amino acids can be substituted, N=19; if any of the four naturally occurring nucleotides can be substituted, N=3), Y=the number of amino acids/nucleotides in the parent sequence that can be substituted (i.e., if the amino acid sequence is 100 aa in length and 10% genetic variation is allowed, Y=10 [100@10%]), and X=the total sequence length of the sequence of interest.
2 These calculations were performed as follows: TV=(NY)(X!)/(Y!)((X-Y-1)!), wherein, TV=the total number of variant sequences, N=the number of amino acids or nucleotides that can be substituted (i.e., if any of the 20 naturally occurring amino acids can be substituted, N=19; if any of the four naturally occurring nucleotides can be substituted, N=3), Y=the number of amino acids/nucleotides in the parent sequence that can be substituted (i.e., if the amino acid sequence is 100 aa in length and 10% genetic variation is allowed, Y=10 [100@10%]), and X=the total sequence length of the sequence of interest.