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 .
Detailed Action
This action is in response to the papers filed August 8, 2025.
Amendments
Applicant's amendments, filed August 8, 2025, is acknowledged. Applicant has cancelled Claims 5, 8, and 22-56.
Claims 1-4, 6-7, and 9-21 are pending.
Election/Restrictions
Applicant has elected without traverse the following species, wherein:
i) the alternative Cas protein is SEQ ID NO: 1, as recited in Claim 3;
ii) the alternative localization signal is SEQ ID NO:50, as recited in Claim 6;
iii) the alternative Cas protein nucleic acid is SEQ ID NO:132, as recited in Claim 9, whereby discordant elections between (i), (ii), and (iii) will be considered a non-compliant amendment;
iv) the alternative target virus is coronavirus, as recited in Claims 11 (coronavirus);
v) the alternative virus target gene is coronavirus S2M sequence, as recited in Claim 12, whereby discordant elections between (iv) and (v) will be considered a non-compliant amendment;
vi) the alternative guide is SEQ ID NO:189, as recited in Claim 14, whereby discordant elections between (iv), (v) and (vi) will be considered a non-compliant amendment; and
vii) the alternative DR is SEQ ID NO:267, as recited in Claim 21.
During a telephone conversation with Applicant’s representative, Abigail DiVito Evans, 215-268-3888, on August 12, 2025, the Examiner stated that elected SEQ ID NO:189 is discordant with the prior-elected coronavirus S2M sequence. Thus, for (vi), a different SEQ ID NO is required.
In a voice message August 14, 2025, Applicant’s representative, Abigail DiVito Evans, elected SEQ ID NO:196.
Affirmation of this election must be made by applicant in replying to this Office action.
In light of the cite prior art below, the Examiner rejoins (vi) alternative S2M guide SEQ ID NO’s 196, 176-181, and 221-222.
Claims 1-4, 6-7, and 9-21 are pending.
Claims 7, 10, 13, and 15-18 are pending but withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected invention, there being no allowable generic or linking claim.
Claims 1-4, 6, 9, 11-12, 14, and 19-21 are under consideration.
Priority
This application is a 371 of PCT/US2021/024397 filed on March 26, 2021.
Information Disclosure Statement
Applicant has filed Information Disclosure Statements on August 9, 2025 and October 1, 2025 that have been considered.
The information disclosure statement filed August 9, 2025 and October 1, 2025 fail to comply with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609 because 37 CFR 1.98(b) requires that each item of information in an IDS be identified properly. Each publication must be identified by publisher, author (if any), title, relevant pages of the publication, and date and place of publication. The date of publication supplied must include at least the month and year of publication, except that the year of publication (without the month) will be accepted if the applicant points out in the information disclosure statement that the year of publication is sufficiently earlier than the effective U.S. filing date and any foreign priority date so that the particular month of publication is not in issue.
See also MPEP 707.05(e) for electronic documents, including, but not limited to:
(D) reference to the unique Digital Object Identifier (DOI) number, or other unique identification number, if known.
Bibliographic information provided must be at least enough to identify the publication. author, title and date. For books, minimal information includes the author, title, and date. For periodicals, at least the title of the periodical, the volume number, date, and pages should be given.
NPL citations have been lined through for being defective of one or more requirements.
The signed and initialed PTO Forms 1449 are mailed with this action.
Claim Rejections - 35 USC § 112
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.
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.
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.
1. Claim(s) 11-12 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.
The term “substantially complementary” in Claim 11 is a relative term which renders the claim indefinite. The term “substantially complementary” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
A claim may be rendered indefinite by reference to an object that is variable. (MPEP §2173.05(b)).
The specification discloses “substantially” includes, but is not limited to, 70%-99% (e.g. pg 31, line 32-pg 32, line 3).
If there are multiple ways to measure “substantially complementary”, yet each yields a different result, then the claim may be indefinite because it is unclear which % identity is to be achieved to determine infringement.
The instant claims as a whole do not apprise one of ordinary skill in the art of its scope and, therefore, does not serve the notice function required by 35 U.S.C. 112, second paragraph, by providing clear warning to others as to what constitutes infringement of the patent.
Dependent claims are included in the basis of the rejection because they do not correct the primary deficiencies of the independent claim(s).
2. Claim 14 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Claim 11 recites wherein the viral infection is a coronavirus, and the guide sequence is substantially complementary to the coronavirus.
Claim 12 recites wherein the guide sequence targets the coronavirus S2M sequence (Applicant’s elected species).
Claim 14 recites wherein the guide sequence comprises SEQ ID NO:196 (Applicant’s elected species).
The art recognizes that nucleic acid sequences are written in 5’ to 3’ direction.
SEQ ID NO:196 is disclosed to be:
5’ tgtaatccctcctgaactttctcggtggtg 3’
However, a search of SEQ ID NO:196 fails to identify a corresponding coronavirus target sequence. (Search results available in SLIC.)
Rather, upon further analysis of SEQ ID NO:196, it appears to be the sequence of SEQ ID NO:176, written in 3’ to 5’ direction, which is contradictory to art-recognized lexicography and the genetic code.
SEQ ID NO:176 (5’ to 3’) is:
5’ acattagggaggacttgaaagagccaccac 3’
The reverse-complement of SEQ ID NO:176 (5’ to 3’) is:
5’ gtggtggctctttcaagtcctccctaatgt 3’
SEQ ID NO:196, if in proper 5’ to 3’ form, would be:
5’ gtggtggctctttcaagtcctccctaatgt 3’
Thus, those of ordinary skill in the art would immediately recognize that instant SEQ ID NO:196 is not complementary to a target sequence of the coronavirus S2M because it cannot hybridize to said coronavirus S2M, for failing to be complementary to the coronavirus S2M sequence.
Appropriate correction is required.
3. Claim 14 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.
The Examiner incorporates herein the above 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, rejection.
Because SEQ ID NO:196 is not complementary to a coronavirus S2M target sequence, and those of ordinary skill in the art would immediately recognize that instant SEQ ID NO:196 is not complementary to a target sequence of the coronavirus S2M because it cannot hybridize to said coronavirus S2M, for failing to be complementary to the coronavirus S2M sequence, instant claim fails to further limit Claim 11.
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 § 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 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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103(a) 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.
4. Claims 1-4, 11, and 19-20 are rejected under AIA 35 U.S.C. 103 as being unpatentable over Zhang et al (WO 19/010422; of record) in view of Liu et al (WO 20/014261; of record).
Determining the scope and contents of the prior art, and Ascertaining the differences between the prior art and the claims at issue.
With respect to Claim 1, Zhang et al is considered relevant prior art for having disclosed a CRISPR RNA targeting a viral sequence (e.g. Figure 2A) and Cas proteins comprising a nuclear export signal (e.g. [00123]), wherein the Cas protein may be Cas13 (e.g. [0013]; [0498], “Cas13a….with a nuclear export signal”), e.g. the nuclear export signal LYPERLRRILT (SEQ ID NO:159).
Zhang et al do not disclose wherein the nuclear export signal has an amino acid sequence that is at least 80% identical to SEQ ID NO:58.
However, prior to the effective filing date of the instantly claimed invention, Liu et al is considered relevant prior art for having disclosed a Cas13 protein comprising a nuclear export signal (e.g. [0045]; Figures 17A-B) the nuclear export signal having the amino acid sequence of SEQ ID NO:58, to wit, LQLPPLERLTL (e.g. [00152], SEQ ID NO:34).
Resolving the level of ordinary skill in the pertinent art.
People of the ordinary skill in the art will be highly educated individuals such as medical doctors, scientists, or engineers possessing advanced degrees, including M.D.'s and Ph.D.'s. Thus, these people most likely will be knowledgeable and well-read in the relevant literature and have the practical experience in molecular biology and gene editing technologies. Therefore, the level of ordinary skill in this art is high.
"A person of ordinary skill in the art is also a person of ordinary creativity, not an automaton." KSR International Co. v. Teleflex Inc., 550 U.S. ___, ___, 82 USPQ2d 1385, 1397 (2007). "[I]n many cases a person of ordinary skill will be able to fit the teachings of multiple patents together like pieces of a puzzle." Id. Office personnel may also take into account "the inferences and creative steps that a person of ordinary skill in the art would employ." Id. at ___, 82 USPQ2d at 1396.
Considering objective evidence present in the application indicating obviousness or nonobviousness.
The focus when making a determination of obviousness should be on what a person of ordinary skill in the pertinent art would have known at the time of the invention, and on what such a person would have reasonably expected to have been able to do in view of that knowledge. This is so regardless of whether the source of that knowledge and ability was documentary prior art, general knowledge in the art, or common sense. M.P.E.P. §2141.
The rationale to modify or combine the prior art does not have to be expressly stated in the prior art; the rationale may be expressly or impliedly contained in the prior art or it may be reasoned from knowledge generally available to one of ordinary skill in the art, established scientific principles, or legal precedent established by prior case law. In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988); In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992). See also In re Kotzab, 217 F.3d 1365, 1370, 55 USPQ2d 1313, 1317 (Fed. Cir. 2000) (setting forth test for implicit teachings); In re Eli Lilly & Co., 902 F.2d 943, 14 USPQ2d 1741 (Fed. Cir. 1990) (discussion of reliance on legal precedent); In re Nilssen, 851 F.2d 1401, 1403, 7 USPQ2d 1500, 1502 (Fed. Cir. 1988) (references do not have to explicitly suggest combining teachings); and Ex parte Levengood, 28 USPQ2d 1300 (Bd. Pat. App. & Inter. 1993) (reliance on logic and sound scientific reasoning). See MPEP §2144.
Prior to the effective filing date of the instantly claimed invention, it would have been obvious to one of ordinary skill in the art to substitute a first nuclear export signal with a second nuclear export signal comprising the amino acid sequence of instant SEQ ID NO:58 with a reasonable expectation of success because the simple substitution of one known element for another would have yielded predictable results to one of ordinary skill in the art at the time of the invention. M.P.E.P. §2144.07 states "The selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945).” When substituting equivalents known in the prior art for the same purpose, an express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. In re Fout, 675 F.2d 297, 213 USPQ 532 (CCPA 1982). M.P.E.P. §2144.06. An artisan would be motivated to substitute a first nuclear export signal with a second nuclear export signal comprising the amino acid sequence of instant SEQ ID NO:58 because Liu et al disclose Cas13 proteins comprising a nuclear export signal, whereby the nuclear export signal comprises the amino acid sequence of instant SEQ ID NO:58.
It is proper to "take account of the inferences and creative steps that a person of ordinary skill in the art would employ." KSR Int'l Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741,82 USPQ2d 1385, 1396 (2007). See also Id. At 1742, 82 USPQ2d 1397 ("A person of ordinary skill is also a person of ordinary creativity, not an automaton.").
It should be noted that the KSR case forecloses the argument that a specific teaching, suggestion, or motivation is required to support a finding of obviousness. See the recent Board decision Ex parte Smith, —USPQ2d—, slip op. at 20, (Bd. Pat. App. & Interf. June 25, 2007) (citing KSR, 82 USPQ2d at 1396) (available at http: www. uspto.gov/web/offices/dcom/bpai/prec/fd071925 .pdf).
With respect to Claim 2, Zhang et al disclosed wherein the Cas protein is Cas13 (e.g. Figure 2a; [0013]; Example 2).
Liu et al disclosed wherein the Cas protein is Cas13 (e.g. [0045]).
With respect to Claim 3, Zhang et al disclosed wherein the Cas13 protein comprises an amino acid sequence (SEQ ID NO:48) that is 100% identical to instant SEQ ID NO:1. (Search results available in SLIC.)
With respect to Claim 4, Zhang et al disclosed wherein the Cas protein further comprises a nuclear localization signal (e.g. [0123]).
With respect to Claim 11, Zhang et al disclosed wherein the target viral genome is coronavirus (e.g. [0029]; claim 38), and wherein the target sequence is within a mRNA (e.g. [0085]).
With respect to Claims 19-20, Zhang et al disclosed wherein the crRNA further comprises a direct repeat (DR) sequence located 3’ to the guide sequence (e.g. [00154])
The cited prior art meets the criteria set forth in both Graham and KSR, and the teachings of the cited prior art provide the requisite teachings and motivations with a clear, reasonable expectation of success. Thus, the invention as a whole is prima facie obvious.
5. Claim(s) 3 and 9 are rejected under AIA 35 U.S.C. 103 as being unpatentable over Zhang et al (WO 19/010422; of record) in view of Liu et al (WO 20/014261; of record), as applied to Claims 1-4, 11, and 19-20 above, and in further view of Rodriguez et al (WO 20/079243; published April 23, 2020; filed October 18, 2019; priority to October 18, 2018).
Determining the scope and contents of the prior art, and Ascertaining the differences between the prior art and the claims at issue.
Neither Zhang et al nor Liu et al disclosed wherein the nucleic acid encoding Cas13 comprises a nucleotide sequence that is at least 80% identical to instant SEQ ID NO:132.
However, prior to the effective filing date of the instantly claimed invention, and with respect to Claim 9, Rodriguez et al is considered relevant prior art for having disclosed a nucleic acid encoding Cas13 (SEQ ID NO:127) comprising a nucleotide sequence that is 100% identical to instant SEQ ID NO:132. (Search results available in SLIC.)
Considering objective evidence present in the application indicating obviousness or nonobviousness.
The focus when making a determination of obviousness should be on what a person of ordinary skill in the pertinent art would have known at the time of the invention, and on what such a person would have reasonably expected to have been able to do in view of that knowledge. This is so regardless of whether the source of that knowledge and ability was documentary prior art, general knowledge in the art, or common sense. M.P.E.P. §2141.
The rationale to modify or combine the prior art does not have to be expressly stated in the prior art; the rationale may be expressly or impliedly contained in the prior art or it may be reasoned from knowledge generally available to one of ordinary skill in the art, established scientific principles, or legal precedent established by prior case law. In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988); In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992). See also In re Kotzab, 217 F.3d 1365, 1370, 55 USPQ2d 1313, 1317 (Fed. Cir. 2000) (setting forth test for implicit teachings); In re Eli Lilly & Co., 902 F.2d 943, 14 USPQ2d 1741 (Fed. Cir. 1990) (discussion of reliance on legal precedent); In re Nilssen, 851 F.2d 1401, 1403, 7 USPQ2d 1500, 1502 (Fed. Cir. 1988) (references do not have to explicitly suggest combining teachings); and Ex parte Levengood, 28 USPQ2d 1300 (Bd. Pat. App. & Inter. 1993) (reliance on logic and sound scientific reasoning). See MPEP §2144.
Prior to the effective filing date of the instantly claimed invention, it would have been obvious to one of ordinary skill in the art to substitute a first nucleic acid encoding Cas13 with a second nucleic acid encoding Cas13 comprising the nucleotide sequence of instant SEQ ID NO:132 with a reasonable expectation of success because the simple substitution of one known element for another would have yielded predictable results to one of ordinary skill in the art at the time of the invention. M.P.E.P. §2144.07 states "The selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945).” When substituting equivalents known in the prior art for the same purpose, an express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. In re Fout, 675 F.2d 297, 213 USPQ 532 (CCPA 1982). M.P.E.P. §2144.06. An artisan would be motivated to substitute a first nucleic acid encoding Cas13 with a second nucleic acid encoding Cas13 comprising the nucleotide sequence of instant SEQ ID NO:132 because those of ordinary skill in the art previously recognized the nucleotide sequence of SEQ ID NO:132 encodes Cas13.
It is proper to "take account of the inferences and creative steps that a person of ordinary skill in the art would employ." KSR Int'l Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741,82 USPQ2d 1385, 1396 (2007). See also Id. At 1742, 82 USPQ2d 1397 ("A person of ordinary skill is also a person of ordinary creativity, not an automaton.").
It should be noted that the KSR case forecloses the argument that a specific teaching, suggestion, or motivation is required to support a finding of obviousness. See the recent Board decision Ex parte Smith, —USPQ2d—, slip op. at 20, (Bd. Pat. App. & Interf. June 25, 2007) (citing KSR, 82 USPQ2d at 1396) (available at http: www. uspto.gov/web/offices/dcom/bpai/prec/fd071925 .pdf).
With respect to Claim 3, Zhang et al disclosed wherein the Cas13 protein comprises an amino acid sequence (SEQ ID NO:48) that is 100% identical to instant SEQ ID NO:1. (Search results available in SLIC.)
Rodriguez et al disclosed a nucleic acid encoding Cas13 (SEQ ID NO:127) comprising a nucleotide sequence that is 100% identical to instant SEQ ID NO:132, wherein said SEQ ID NO:127 encodes a Cas13 protein comprising an amino acid sequence that is 100% identical to instant SEQ ID NO:1. (Search results available in SLIC.)
The cited prior art meets the criteria set forth in both Graham and KSR, and the teachings of the cited prior art provide the requisite teachings and motivations with a clear, reasonable expectation of success. Thus, the invention as a whole is prima facie obvious.
6. Claim(s) 21 is rejected under AIA 35 U.S.C. 103 as being unpatentable over Zhang et al (WO 19/010422; of record) in view of Liu et al (WO 20/014261; of record), as applied to Claims 1-4, 11, and 19-20 above, and in further view of Gootenberg et al (U.S. 2020/0231975).
Determining the scope and contents of the prior art, and Ascertaining the differences between the prior art and the claims at issue.
Neither Zhang et al nor Liu et al disclosed wherein the direct repeat comprises a nucleotide sequence that is 100% identical to instant SEQ ID NO:267.
However, prior to the effective filing date of the instantly claimed invention, and with respect to Claim 21, Gootenberg et al is considered relevant prior art for having disclosed direct repeats for Cas13 guide RNAs, wherein the DR comprises a nucleotide sequence (SEQ ID NO:83; 0137]) that is 100% identical to instant SEQ ID NO:267, as shown below:
GTTGTGGAAGGTCCAGTTTTGAGGGGCTATTACAAC
||||||||||||||||||||||||||||||||||||
GTTGTGGAAGGTCCAGTTTTGAGGGGCTATTACAAC.
Considering objective evidence present in the application indicating obviousness or nonobviousness.
The focus when making a determination of obviousness should be on what a person of ordinary skill in the pertinent art would have known at the time of the invention, and on what such a person would have reasonably expected to have been able to do in view of that knowledge. This is so regardless of whether the source of that knowledge and ability was documentary prior art, general knowledge in the art, or common sense. M.P.E.P. §2141.
The rationale to modify or combine the prior art does not have to be expressly stated in the prior art; the rationale may be expressly or impliedly contained in the prior art or it may be reasoned from knowledge generally available to one of ordinary skill in the art, established scientific principles, or legal precedent established by prior case law. In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988); In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992). See also In re Kotzab, 217 F.3d 1365, 1370, 55 USPQ2d 1313, 1317 (Fed. Cir. 2000) (setting forth test for implicit teachings); In re Eli Lilly & Co., 902 F.2d 943, 14 USPQ2d 1741 (Fed. Cir. 1990) (discussion of reliance on legal precedent); In re Nilssen, 851 F.2d 1401, 1403, 7 USPQ2d 1500, 1502 (Fed. Cir. 1988) (references do not have to explicitly suggest combining teachings); and Ex parte Levengood, 28 USPQ2d 1300 (Bd. Pat. App. & Inter. 1993) (reliance on logic and sound scientific reasoning). See MPEP §2144.
Prior to the effective filing date of the instantly claimed invention, it would have been obvious to one of ordinary skill in the art to substitute a first Cas13 crRNA DR sequence with a second Cas13 crRNA DR sequence comprising the nucleotide sequence of instant SEQ ID NO:267 with a reasonable expectation of success because the simple substitution of one known element for another would have yielded predictable results to one of ordinary skill in the art at the time of the invention. M.P.E.P. §2144.07 states "The selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945).” When substituting equivalents known in the prior art for the same purpose, an express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. In re Fout, 675 F.2d 297, 213 USPQ 532 (CCPA 1982). M.P.E.P. §2144.06. An artisan would be motivated to substitute a first Cas13 crRNA DR sequence with a second Cas13 crRNA DR sequence comprising the nucleotide sequence of instant SEQ ID NO:267 because Gootenberg et al disclosed that Cas13 uses crRNAs comprise a DR sequence comprising the nucleotide sequence of instant SEQ ID NO:267.
It is proper to "take account of the inferences and creative steps that a person of ordinary skill in the art would employ." KSR Int'l Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741,82 USPQ2d 1385, 1396 (2007). See also Id. At 1742, 82 USPQ2d 1397 ("A person of ordinary skill is also a person of ordinary creativity, not an automaton.").
It should be noted that the KSR case forecloses the argument that a specific teaching, suggestion, or motivation is required to support a finding of obviousness. See the recent Board decision Ex parte Smith, —USPQ2d—, slip op. at 20, (Bd. Pat. App. & Interf. June 25, 2007) (citing KSR, 82 USPQ2d at 1396) (available at http: www. uspto.gov/web/offices/dcom/bpai/prec/fd071925 .pdf).
The cited prior art meets the criteria set forth in both Graham and KSR, and the teachings of the cited prior art provide the requisite teachings and motivations with a clear, reasonable expectation of success. Thus, the invention as a whole is prima facie obvious.
7. Claim(s) 4 and 6 are rejected under AIA 35 U.S.C. 103 as being unpatentable over Zhang et al (WO 19/010422; of record) in view of Liu et al (WO 20/014261; of record), as applied to Claims 1-4, 11, and 19-20 above, and in further view of Bridier-Nahmias et al (U.S. 2018/0022781).
Determining the scope and contents of the prior art, and Ascertaining the differences between the prior art and the claims at issue.
Neither Zhang et al nor Liu et al disclosed wherein the NLS comprises an amino acid sequence that is at least 80% identical to instant SEQ ID NO:50.
However, prior to the effective filing date of the instantly claimed invention, and with respect to Claim 6, Bridier-Nahmias et al is considered relevant prior art for having disclosed a nuclear localization amino acid sequence (SEQ ID NO:12; Figure 5) comprising an amino acid sequence that is 100% identical to instant SEQ ID NO:50, as shown below:
NSKKRSLEDNETEIKVSRDTWNTKNMRSLEPPRSKKRIH
|||||||||||||||||||||||||||||||||||||||
NSKKRSLEDNETEIKVSRDTWNTKNMRSLEPPRSKKRIH
Considering objective evidence present in the application indicating obviousness or nonobviousness.
The focus when making a determination of obviousness should be on what a person of ordinary skill in the pertinent art would have known at the time of the invention, and on what such a person would have reasonably expected to have been able to do in view of that knowledge. This is so regardless of whether the source of that knowledge and ability was documentary prior art, general knowledge in the art, or common sense. M.P.E.P. §2141.
The rationale to modify or combine the prior art does not have to be expressly stated in the prior art; the rationale may be expressly or impliedly contained in the prior art or it may be reasoned from knowledge generally available to one of ordinary skill in the art, established scientific principles, or legal precedent established by prior case law. In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988); In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992). See also In re Kotzab, 217 F.3d 1365, 1370, 55 USPQ2d 1313, 1317 (Fed. Cir. 2000) (setting forth test for implicit teachings); In re Eli Lilly & Co., 902 F.2d 943, 14 USPQ2d 1741 (Fed. Cir. 1990) (discussion of reliance on legal precedent); In re Nilssen, 851 F.2d 1401, 1403, 7 USPQ2d 1500, 1502 (Fed. Cir. 1988) (references do not have to explicitly suggest combining teachings); and Ex parte Levengood, 28 USPQ2d 1300 (Bd. Pat. App. & Inter. 1993) (reliance on logic and sound scientific reasoning). See MPEP §2144.
Prior to the effective filing date of the instantly claimed invention, it would have been obvious to one of ordinary skill in the art to substitute a first nuclear localization signal with a second nuclear localization signal comprising the amino acid sequence of instant SEQ ID NO:50 with a reasonable expectation of success because the simple substitution of one known element for another would have yielded predictable results to one of ordinary skill in the art at the time of the invention. M.P.E.P. §2144.07 states "The selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945).” When substituting equivalents known in the prior art for the same purpose, an express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. In re Fout, 675 F.2d 297, 213 USPQ 532 (CCPA 1982). M.P.E.P. §2144.06. An artisan would be motivated to substitute a first nuclear localization signal with a second nuclear localization signal comprising the amino acid sequence of instant SEQ ID NO:50 because Bridier-Nahmias et al disclosed that chimeric proteins comprising nucleic acid binding domains (e.g. Abstract) may comprise a nuclear localization signal comprising the amino acid sequence of instant SEQ ID NO:50.
It is proper to "take account of the inferences and creative steps that a person of ordinary skill in the art would employ." KSR Int'l Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741,82 USPQ2d 1385, 1396 (2007). See also Id. At 1742, 82 USPQ2d 1397 ("A person of ordinary skill is also a person of ordinary creativity, not an automaton.").
It should be noted that the KSR case forecloses the argument that a specific teaching, suggestion, or motivation is required to support a finding of obviousness. See the recent Board decision Ex parte Smith, —USPQ2d—, slip op. at 20, (Bd. Pat. App. & Interf. June 25, 2007) (citing KSR, 82 USPQ2d at 1396) (available at http: www. uspto.gov/web/offices/dcom/bpai/prec/fd071925 .pdf).
The cited prior art meets the criteria set forth in both Graham and KSR, and the teachings of the cited prior art provide the requisite teachings and motivations with a clear, reasonable expectation of success. Thus, the invention as a whole is prima facie obvious.
8. Claim(s) 12 and 14 are rejected under AIA 35 U.S.C. 103 as being unpatentable over Zhang et al (WO 19/010422; of record) in view of Liu et al (WO 20/014261; of record), as applied to Claims 1-4, 11, and 19-20 above, and in further view of Saigo et al (U.S. 2011/0033860), Abbott et al (Development of CRISPR as a prophylactic strategy to combat novel coronavirus and influenza, bioRxiv preprint, 20 pages, doi.org/10.1101/2020.03.13.991307; available online March 14, 2020), and Ahmed et al (A Comprehensive Analysis of cis-Acting RNA Elements in the SARS-CoV-2 Genome by a Bioinformatics Approach, Frontiers in Genetics e572702, 18 pages, doi: 10.3389/fgene.2020.572702; available online December 23, 2020).
Determining the scope and contents of the prior art, and Ascertaining the differences between the prior art and the claims at issue.
Neither Zhang et al nor Liu et al disclosed wherein the CRISPR/Cas system is directed to the coronavirus S2M element.
However, prior to the effective filing date of the instantly claimed invention, Saigo et al is considered relevant prior art for having disclosed designing siRNA against coronavirus S2M motif (e.g. [0262]; Table 10).
Siago et al disclosed s2m motif; SARS-29606; gatcgagggtacagtgaat (SEQ ID NO:46), which is:
86% identical to, and substantially overlaps with instant SEQ ID NO:181 and 222 (lower); and
55% identical to, and substantially overlaps with instant SEQ ID NO:221 (lower), as shown below:
GATCGAGGGTACAGTGAA
||||||| ||||||||||
GATCGAGTGTACAGTGAA
GATCGAGGGTAC
||||||| ||||
GATCGAGTGTAC
Saigo et al do not disclose a CRISPR/Cas system directed against coronavirus.
However, prior to the effective filing date of the instantly claimed invention, Abbott et al is considered relevant prior art for having taught the use of the CRISPR/Cas13 system to degrade SARS-CoV-2 sequences using crRNAs targeting conserved viral regions (e.g. Abstract), resulting in a collection of 3,203 crRNAs.
Abbott taught 3’ crRNAs (Supplemental Table 1, nCov_crRNA24594-24609) that target the coronavirus S2M motif and substantially overlap with and/or touch instant SIN:221 and 222, as shown below (SEQ ID NO:221, upper):
TACTCCGCGTGGCCTCG
TACTCCGCGTGGCCTCGGTGAAAATGTGGTGGCTCTT
TACTCCGCGTGGCCTCGGTGAAAATGTGGTGGCTCTT
TACTCCGCGTGGCCTCGGTGAAAATGTGGTGGCTCTT
TACTCCGCGTGGCCTCGGTGAAAATGTGGTGGCTCTT
TACTCCGCGTGGCCTCGGTGAAAATGTGGTGGCTCTT
TACTCCGCGTGGCCTCGGTGAAAATGTGGTGGCTCTT
TACTCCGCGTGGCCTCGGTGAAAATGTGGTGGCTCTT
TACTCCGCGTGGCCTCGGTGAAAATGTGGTGGCTCTT
TACTCCGCGTGGCCTCGGTGAAAATGTGGTGGCTCTT
TACTCCGCGTGGCCTCGGTGAAAATGTGGTGGCTCTT
TACTCCGCGTGGCCTCGGTGAAAATGTGGTGGCTCTT
TACTCCGCGTGGCCTCGGTGAAAATGTGGTGGCTCTT
TACTCCGCGTGGCCTCGGTGAAAATGTGGTGGCTCTT
TACTCCGCGTGGCCTCGGTGAAAATGTGGTGGCTCTT
TACTCCGCGTGGCCTCGGTGAAAATGTGGTGGCTCTT
TACTCCGCGTGGCCTCGGTGAAAATGTGGTGGCTCTT
TACTCCGCGTGGCCTCGGTGAAAATGTGGTGGCTCTT
Ahmed et al is considered relevant prior art for having taught that the coronavirus S2M is an important cis-acting RNA element highly conserved across most studied coronaviruses (e.g. pg 1, introduction). Ahmed et al taught that the prior art recognized the S2M is involved in viral replication and packaging, and that it is a potential target for antivirus therapeutics (e.g. pg 15, col. 1).
Ahmed et al taught a S2M nucleotide sequence (e.g. Table 2; Figure 6a).
TTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAAC,
which is the reverse-complement of, and substantially overlaps with, Abbott et al’s S2M region.
Instant SEQ ID NO’s:177, 178, 179, 180, and 181 are substantially identical to and overlap with the S2M nucleotide sequence of Ahmed et al, as shown below:
Instant SEQ ID NO’s:176 is substantially identical to and overlaps with SEQ ID NO’s 177-179, and substantially touches (2nt space) the S2M nucleotide sequence of Ahmed et al, as shown below:
TTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAAC
acgcggagtacgatcgagtgtacagtgaac (181)
attttcaccaggccacgcggagtacgatc (180)
agagccaccacattttcaccaggccacgc (179)
TTTCACCGAGGCCACGCGGAGTACGATC
ttgaaagagccaccacattttcaccaggc (178)
gggaggacttgaaagagccaccacattttc (177)
acattagggaggacttgaaagagccaccac (176)
Considering objective evidence present in the application indicating obviousness or nonobviousness.
The focus when making a determination of obviousness should be on what a person of ordinary skill in the pertinent art would have known at the time of the invention, and on what such a person would have reasonably expected to have been able to do in view of that knowledge. This is so regardless of whether the source of that knowledge and ability was documentary prior art, general knowledge in the art, or common sense. M.P.E.P. §2141.
The rationale to modify or combine the prior art does not have to be expressly stated in the prior art; the rationale may be expressly or impliedly contained in the prior art or it may be reasoned from knowledge generally available to one of ordinary skill in the art, established scientific principles, or legal precedent established by prior case law. In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988); In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992). See also In re Kotzab, 217 F.3d 1365, 1370, 55 USPQ2d 1313, 1317 (Fed. Cir. 2000) (setting forth test for implicit teachings); In re Eli Lilly & Co., 902 F.2d 943, 14 USPQ2d 1741 (Fed. Cir. 1990) (discussion of reliance on legal precedent); In re Nilssen, 851 F.2d 1401, 1403, 7 USPQ2d 1500, 1502 (Fed. Cir. 1988) (references do not have to explicitly suggest combining teachings); and Ex parte Levengood, 28 USPQ2d 1300 (Bd. Pat. App. & Inter. 1993) (reliance on logic and sound scientific reasoning). See MPEP §2144.
Prior to the effective filing date of the instantly claimed invention, it would have been obvious to one of ordinary skill in the art to arrive at a method of treating a coronavirus infection using a therapeutic nucleic acid directed against the coronavirus S2M motif with a reasonable expectation of success because those of ordinary skill in the art previously recognized the scientific and technical concepts that:
i) S2M is involved in viral replication and packaging, and that it is a potential target for antivirus therapeutics (Ahmed et al);
ii) siRNA directed against S2M and having a nucleotide sequence substantially similar to and/or overlapping with instant SEQ ID NO:181, 221, and 222 crRNAs was previously known and successfully reduced to practice as an antiviral (Saigo et al); and
iii) Cas13 crRNAs directed against conserved regions of the coronavirus genome, including S2M, and having a nucleotide sequence substantially similar to and/or overlapping with instant SEQ ID NO:221, and 222 crRNAs was previously known (Abbott et al).
In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). It is routine procedure to optimize component amounts to arrive at an optimal product that is superior for its intended use, since it has been held where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are close enough that one skilled in the art would have expected them to have the same properties. See M.P.E.P. §2144.05(I).
Instant specification fails to disclose an element of criticality for an S2M crRNA nucleotide sequence that is substantially identical to and/or overlaps with the prior art S2M siRNA and/or crRNA target nucleotide sequences.
It is proper to "take account of the inferences and creative steps that a person of ordinary skill in the art would employ." KSR Int'l Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741,82 USPQ2d 1385, 1396 (2007). See also Id. At 1742, 82 USPQ2d 1397 ("A person of ordinary skill is also a person of ordinary creativity, not an automaton.").
It should be noted that the KSR case forecloses the argument that a specific teaching, suggestion, or motivation is required to support a finding of obviousness. See the recent Board decision Ex parte Smith, —USPQ2d—, slip op. at 20, (Bd. Pat. App. & Interf. June 25, 2007) (citing KSR, 82 USPQ2d at 1396) (available at http: www. uspto.gov/web/offices/dcom/bpai/prec/fd071925 .pdf).
The cited prior art meets the criteria set forth in both Graham and KSR, and the teachings of the cited prior art provide the requisite teachings and motivations with a clear, reasonable expectation of success. Thus, the invention as a whole is prima facie obvious.
Conclusion
9. No claims are allowed.
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KEVIN K. HILL
Examiner
Art Unit 1638
/KEVIN K HILL/Primary Examiner, Art Unit 1638