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 Group I (claims 1, 3-5, 8, 11-12, and new claim 32) in the reply filed on October 22, 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)).
However, it is noted that an inadvertent error listed claim 31 with Group I, rather than with Group V (claims 29-30). A telephone call was placed to Dr. Ming Zhang to clarify the Restriction Requirement and place claim 31 correctly with Group V (see the attached Interview Summary).
In addition, in the Reply to the Restriction Requirement, Applicants canceled claims 2, 6-7, 8-9, 13-16, 18-29, amended claims 1, 3-5, 8, 11-12, 17, and 30-31, and added new claim 32.
Thus, claims 17 and 30-31 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 October 22, 2025.
Claims 1, 3-5, 8, 11-12, and 32 are under examination.
Information Disclosure Statement
The Information Disclosure Statements (3) filed October 6, 2021 have been considered.
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 of the following informalities:
All genus and species names in the specification should be italicized.
At paragraph [0081], the first occurrence of “HEPN” should be changed to “Higher Eukaryotes and Prokaryotes Nucleotide-binding domain (HEPN).”
Appropriate correction is required.
The use of the terms NOVABLUE® at paragraph [0463], MINELUTE® at paragraph [0464], HISCRIBE® at paragraphs [0464]-[0465], MEGACLEAR® at paragraph [0464], NASBA® at paragraph [0466], STERICUP® at paragraph [0470], SEPHAROSE® at paragraph [0470], HITRAP® at paragraph [0470], TAQMAN® at paragraphs [0473] and [0513], SYBR® at paragraph [0474], GLUTAMAX® at paragraph [0475], QIAAMP® at paragraph [0476], SUPERSCRIPT® at paragraph [0476], TRITON® at paragraph [0477], DNEASY® at paragraph [0479], QUANT-IT® at paragraph [0479], QUBIT® at paragraph [0479], PURELYSE® at paragraph [0480], QX200® at paragraph [0481], and TWISTDX® at paragraph [0487], which str trade names or marks used in commerce, has been noted in this application. The terms should be accompanied by the generic terminology; furthermore the terms should be capitalized wherever they appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Objections
Claims 5 and 12 are objected to because of the following informalities:
At claim 5, line 27, “HEPN” should be changed to “Higher Eukaryotes and Prokaryotes Nucleotide-binding domain (HEPN).”
At claim 5, line 28, “compris” should be changed to “comprise.”
At claim 5, line 29, “RxxxH” should be changed to “RxxxxH.”
At claim 12, line 21, “mutation confers” should be changed to “mutations confer.”
Appropriate correction is required.
Claim Interpretation
The following is a quotation of 35 U.S.C. 112(f):
(f) Element in Claim for a Combination. – An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The following is a quotation of pre-AIA 35 U.S.C. 112, sixth paragraph:
An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art. The broadest reasonable interpretation of a claim element (also commonly referred to as a claim limitation) is limited by the description in the specification when 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is invoked.
As explained in MPEP § 2181, subsection I, claim limitations that meet the following three-prong test will be interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph:
(A) the claim limitation uses the term “means” or “step” or a term used as a substitute for “means” that is a generic placeholder (also called a nonce term or a non-structural term having no specific structural meaning) for performing the claimed function;
(B) the term “means” or “step” or the generic placeholder is modified by functional language, typically, but not always linked by the transition word “for” (e.g., “means for”) or another linking word or phrase, such as “configured to” or “so that”; and
(C) the term “means” or “step” or the generic placeholder is not modified by sufficient structure, material, or acts for performing the claimed function.
Use of the word “means” (or “step”) in a claim with functional language creates a rebuttable presumption that the claim limitation is to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites sufficient structure, material, or acts to entirely perform the recited function.
Absence of the word “means” (or “step”) in a claim creates a rebuttable presumption that the claim limitation is not to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is not interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites function without reciting sufficient structure, material or acts to entirely perform the recited function.
Claim limitations in this application that use the word “means” (or “step”) are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action. Conversely, claim limitations in this application that do not use the word “means” (or “step”) are not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action.
This application includes one or more claim limitations that do not use the word “means,” but are nonetheless being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, because the claim limitation uses a generic placeholder that is coupled with functional language without reciting sufficient structure to perform the recited function and the generic placeholder is not preceded by a structural modifier. Such claim limitation is: “the kit is configured for point-of-care diagnostic applications” in claim 4.
Because this claim limitation is being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, it is being interpreted to cover the corresponding structure described in the specification as performing the claimed function, and equivalents thereof.
If applicant does not intend to have this limitation interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, applicant may: (1) amend the claim limitation to avoid it being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph (e.g., by reciting sufficient structure to perform the claimed function); or (2) present a sufficient showing that the claim limitation recites sufficient structure to perform the claimed function so as to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph.
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.
Claim 4 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 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.
The claims comprises a limitation that invokes 35 U.S.C. 112(f), but the specification does not link structure to function. Thus, the specification does not disclose adequate structure to perform the claimed functions.
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, 3-5, 8, 11-12, and 32 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.
Regarding claim 4, the claim limitation “the kit is configured for point-of-care diagnostic applications” invokes 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. However, the written description fails to disclose the corresponding structure, material, or acts for performing the entire claimed function and to clearly link the structure, material, or acts to the function. Therefore, the claims are indefinite and is rejected under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph.
Applicant may:
(a) Amend the claim so that the claim limitation will no longer be interpreted as a limitation under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph;
(b) Amend the written description of the specification such that it expressly recites what structure, material, or acts perform the entire claimed function, without introducing any new matter (35 U.S.C. 132(a)); or
(c) Amend the written description of the specification such that it clearly links the structure, material, or acts disclosed therein to the function recited in the claim, without introducing any new matter (35 U.S.C. 132(a)).
If applicant is of the opinion that the written description of the specification already implicitly or inherently discloses the corresponding structure, material, or acts and clearly links them to the function so that one of ordinary skill in the art would recognize what structure, material, or acts perform the claimed function, applicant should clarify the record by either:
(a) Amending the written description of the specification such that it expressly recites the corresponding structure, material, or acts for performing the claimed function and clearly links or associates the structure, material, or acts to the claimed function, without introducing any new matter (35 U.S.C. 132(a)); or
(b) Stating on the record what the corresponding structure, material, or acts, which are implicitly or inherently set forth in the written description of the specification, perform the claimed function. For more information, see 37 CFR 1.75(d) and MPEP §§ 608.01(o) and 2181.
At claim 1, line 2, it is not clear what is meant by the phrase “corresponding target molecules.” To what do these target molecules correspond? Are there any characteristics or sequences that must be present in order for the guide to bind to a target molecule?
Claims 3-5, 8, 11-12, and 32 depend from claim 1, and are therefore included in this rejection.
At claim 3, line 2, it is not clear what is meant by the phrase “corresponding target molecules.” To what do these target molecules correspond? Are there any characteristics or sequences that must be present in order for the guide to bind to a target molecule?
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).
In the present instance, claim 5 recites the broad recitation “wherein the CRISPR RNA-targeting effector is C2c2”, and the claim also recites “preferably wherein the C2c2 is within 20kb of a Cas1 gene” at lines 3-4, which is the narrower statement of the range/limitation. The claim is 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.
In the present instance, claim 5 recites the broad recitation “wherein the C2c2effector protein is from an organism of a genus selected from the group consisting of: Leptorichia. . . and Lachnospira”, and the claim also recites “preferably wherein the C2c2 is from an organism selected from the group consisting of: Leptotrichia shahii. . . and Insolitispirillum peregrinum” and “more preferably wherein the C2c2 effector protein is a L. wadei. . . protein” at lines 5-26, which are the narrower statements of the range/limitation. The claim is 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.
In the present instance, claim 5 recites the broad recitation “wherein the RNA-targeting effector protein comprises one or more HEPN domains”, and the claim also recites “preferably wherein the one or more HEPN domains comprise a RxxxxH motif,” “more preferably wherein the RxxxH motif comprises a R{N/H/K]X1X2C3H sequence,” and “more preferably, where in X1 is R. . . or A” at lines 27-31, which are the narrower statements of the range/limitation. The claim is 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.
In the present instance, claim 8 recites the broad recitation “wherein the RNA-based masking construct suppresses. . . signal”, and the claim also recites “preferably wherein the RNA-based masking construct suppresses . . . negative signal instead” at lines 2-5, which is the narrower statement of the range/limitation. The claim is 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.
Claim 8 recites the limitation "solution" in line 17. There is insufficient antecedent basis for this limitation in the claim.
In the present instance, claim 8 recites the broad recitation “the nanoparticle is a colloidal metal”, and the claim also recites “preferably wherein the colloidal metal is colloidal gold” at line 36-37which is the narrower statement of the range/limitation. The claim is 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.
In the present instance, claim 8 recites the broad recitation “wherein the aptamer sequesters an enzyme”, and the claim also recites “optionally wherein the enzyme is thrombin, horseradish peroxidase, beta-galactosidase, or calf alkaline phosphatase,” and “preferably wherein the is thrombin” at lines 30 and 41-44 which are the narrower statements of the range/limitation. The claim is 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.
At claim 11, line 3, it is not clear if the information within the parentheses is intended to be a claim limitation or not.
In the present instance, claim 11 recites the broad recitation “wherein said SNP or other single nucleotide variation in said guide RNA is at position 3, 4, 5, or 6 of the spacer”, and the claim also recites “preferably position 3” at lines 6-7, which is the narrower statement of the range/limitation. The claim is 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.
In the present instance, claim 11 recites the broad recitation “wherein said mismatch in said guide RNA is at position 1. . . or 9 of the spacer”, and the claim also recites “preferably position 5” at lines 8-9, which is the narrower statement of the range/limitation. The claim is 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.
In the present instance, claim 11 recites the broad recitation “wherein said mismatch is 1, 2, 3, 4, or 5 nucleotides . . . downstream”, and the claim also recites “preferably 2 nucleotides” and “preferably downstream of said SNP . . . in said guide RNA” at lines 1-13, which are the narrower statements of the range/limitation. The claim is 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.
In the present instance, claim 11 recites the broad recitation “wherein said guide RNA comprises a spacer which comprises less than 28 nucleotides”, and the claim also recites “between and including 20-27 nucleotides” which is the narrower statement of the range/limitation. The claim is 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. In addition, it is noted that the phrase “less than 28 nucleotides” includes 0 nucleotides, which implies that there is no spacer present.
In the present instance, claim 11 recites the broad recitation “wherein said guide RNA comprises a spacer which consists of 20-35 nucleotides or 20-23 nucleotides” and the claim also recites “preferably 20 or 23 nucleotides” at lines 17-18 which is the narrower statement of the range/limitation. The claim is 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. In addition, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
In the present instance, claim 12 recites the broad recitation “wherein the one or more guide RNAs. . . that are diagnostic for a disease state” at lines 9-10 and the claim also recites “optionally wherein the disease state is an infection, an organ disease, . . . or an environmentally-acquired disease” and “optionally where the disease state is cancer” at lines 15-19, which are the narrower statements of the range/limitation. The claim is 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.
At claim 12, lines 37-38 and 45, is not clear if the information in the parentheses is intended to be a claim limitation or not.
In the present instance, claim 12 recites the broad recitation “wherein the disease state is a pregnancy or childbirth-related disease” at line 41, and the claim also recites “optionally wherein the pregnancy or childbirth-related disease is selected from the group consisting of . . . and Wolf-Hirschorn Syndrome” which is the narrower statement of the range/limitation. The claim is 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.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 3-4, 8, and 11-12 are rejected under 35 U.S.C. 103 as being unpatentable over Doudna et al. (U.S. Patent Application Publication No. 2017/0362644, published December 21, 2017, claiming priority to U.S. Provisional Patent Application Nos. 62/351,172 and 62/378,156, filed June 16, 2016 and August 22, 2016, respectively, and cited in the Information Disclosure Statement filed October 6, 2021) in view of Severinov et al. (U.S. Patent Application Publication No. 2017/0321198, published November 9, 2017, and claiming priority to PCT Patent Application Publication No. PCT/US2016/038258 and U.S. Provisional Patent Application Nos. 62/181,675, 62/285,349, 62/296,522, and 62/320,231, filed June 17, 2016, June 18, 2015, October 22, 2015, February 17, 2016, and April 8, 2016, respectively), Chien et al. (Proceedings of the 1st IEEE International Conference on Nano/Micro Engineered and Molecular Systems 278-282 (January, 2006), Shafiee et al. (5 Scientific Reports 8719, 1-9 (March 6, 2015), and cited in the Information Disclosure Statement filed October 6, 2021), and Liu et al. (5(8) Advanced Healthcare Materials 871-888 (April 2016)).
Regarding claim 1, Doudna discloses a system for detecting single-stranded target RNA comprising a C2c2 (i.e., cas13a) guide RNA array of two or more guide RNAs, each with a different sequence, and a labeled detector RNA (paragraphs [0094]-[0095], 0122] and [0265]).
Regarding claim 5, Doudna discloses a system for detecting single-stranded target RNA comprising a C2c2 (paragraphs [0094]-[0095], 0122] and [0265]). Doudna discloses that the kit can also include the C2c2 (i.e., Cas13a) protein (paragraph [0267]). Doudna discloses that the C2c2 comprises one or more HEPN domains, which have an RxxxxH motif sequence having the claimed sequences (paragraphs [0050], [0096], [0424], [0428] and Figures 41A-41B). Doudna discloses that the C2c2 protein can be obtained from Leptotrichia species (paragraphs [0193]-[0195]).
Regarding claim 8, Doudna discloses that the detector RNA comprises a fluorescence-emitting dye pair, such as a quencher/fluor pair (paragraph [0266]). Doudna discloses that a fluorescent label may be FITC (paragraphs [0289]-[0291]). Doudna discloses that the system can be used to detect a nucleic acid target sequence in vitro, where the quencher/fluor pair is activated and the nucleic acid is detected (paragraph [0123]). Doudna shows higher cleavage at the higher temperature of 37 °C, which is interpreted as requiring a heating element to heat the reaction of a predetermined temperature (Figure 19B). Doudna discloses the use of an affinity tag for the C2c2 (paragraph [0459]).
Doudna fails to disclose or suggest inclusion of amplification reagents in the system. Doudna fails to disclose or suggest the detection of DNA or polypeptides using the Cas13 program. Doudna fails to disclose or suggest use of multiple CRISPR systems. Doudna fails to disclose or suggest performing a detection/diagnostic method.
Regarding claim 1, Severinov discloses systems comprising C2c2 (Cas13a) for detecting RNA (paragraphs [0084] and [0337]-[0340]). Severinov discloses that the detection of the nucleic acid can be visualized using a split fluorescent protein (paragraph [0338]). Severinov discloses that the system can also be used to target DNA and protein (paragraphs [0018] and [0270]-[0272]). Severinov discloses that the system can be used to target sequences associated with diseases (i.e., the system can be a diagnostic system) (paragraphs [0290]-[0292], [0300]-[0304], and [0308]-[0311]).
Regarding claim 4, Severinov discloses use of amplification reagents including polymerases for polymerase chain reaction (i.e., nucleic acid sequenced-based amplification (paragraph [0730]). Severinov discloses the use of primers, RNA polymerase and an RNA polymerase promoter, (paragraphs [0384], [0715], and [0730]).
Regarding claim 5, Severinov discloses that a Cas1 protein may cluster with the C2c2 locus, which is interpreted as being within 20 kb of each other (paragraphs [0063]-[0064]). Severinov discloses that the C2c2 may be obtained from Leptotrichia wadei F0179 (paragraph [1002]).
Regarding claims 11-12, Severinov discloses that the system can be used to detect single nucleotide polymorphisms (SNPs) (paragraphs [0830] and [0864]-[0985]). Severinov discloses that the C2c2 comprises one or more HEPN domains, which have an RxxxxH motif sequence having the claimed sequences (paragraph [0066] and Figures 11 and 13B).
Regarding claim 3, Chien discloses methods and systems for detecting DNA using a radio frequency identification (RFID) system (abstract). Chien discloses that the target DNA and probe DNA are immobilized on a substrate (abstract). Chien discloses that the system is a lab-on-a-chip (LOC) system (abstract).
Regarding claim 3, Shafiee discloses that paper and flexible substrates can be used in diagnostic assays (abstract). Shafiee discloses that the system can employ biotinylated antibodies, which can be captured using streptavidin coated beads (Figure 1).
Regarding claim 3, Liu discloses microfluidic devices that can be used as a lab-on-a-chip (LOC) device, paragraph bridging pages 1 and 2). Liu discloses that because of the small dimensions, it is easy to transfer (move) and heat, which is interpreted as including a movable heating block, and which enables faster reaction and detection (page 2, first full paragraph). Liu discloses that nucleic acids can be detected using microfluidic devices (page 4, first three full paragraphs). Liu discloses that the system can employ individual droplets, each having a reaction volume (pages 9-10).
It would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention to use Doudna’s CRISPR/Cas13 detection system to detect Severinov’s DNA and/or polypeptides because this provides additional methodology for the detection of a wide variety of nucleic acids, which can be used in both diagnostic and therapeutic applications.
It would also have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention to include Severinov’s amplification reagents, primers, polymerase, and polymerase promoters in the system of Doudna because this provides a way to increase target DNA and/or RNA molecules, which in turn provides for a more sensitive, reproducible, and accurate nucleic acid detection system.
It would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention to use the detection systems and devices disclosed by Chien, Shafiee, and Liu for automating the detection systems disclosed and suggested by Doudna and Severinov because the devices and systems disclosed by Chien, Shafiee, and Liu provide for a simple, cost-effective, accurate, and reproducible automation of the C2c2 detection systems of Doudna and Severinov.
Claims 5 and 32 are rejected under 35 U.S.C. 103 as being unpatentable over Doudna in view of Severinov, Chien, Shafiee, and Liu, as applied to claimed 1, 3-4, 8, and 11-12 above, and further in view of Pardee et al. (165 Cell 1255-1266 (2016), and cited in the Information Disclosure Statement filed October 6, 2021).
Doudna, Severinov, Chien, Shafiee, and Liu discloses a nucleic acid diagnostic kit comprising a CRISPR system, as discussed above.
Doudna, Severinov, Chien, Shafiee, and Liu fail to disclose freeze-drying the CRISPR diagnostic kit components that can be used as a point-of-care application.
Pardee discloses a method of detecting/diagnosing Zika virus using biomolecular sensors and a CRISRP-based technology (abstract). Pardee discloses that the CRISPR-Cas9 system can be used as a molecular diagnostic in the field (abstract). Pardee discloses that a solid substrate, paper system can distinguish between Zika and Dengue RNA sequences (page 1260, column 2, first full paragraph). Pardee discloses that CRISPR-Cas9 is compatible with lyophilization, thus being usable in the field (page 1260, column 2, first full paragraph).
It would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention to lyophilize the C2c2 CRISPR system disclosed and suggested by Doudna, Severinov, Chien, Shafiee, and Liu, in order for the diagnostic kit to be transported and employed in the field, as disclosed by Pardee. Because CRISPR diagnostic system components can be lyophilized, one of ordinary skill in the art would have a predictable and reasonable expectation of success in using Pardee’s lyophilization of CRISPR for the C2c2 diagnostic system of Doudna, Severinov, Chien, Shafiee, and Liu. One of ordinary skill in the art would have been motivated to lyophilize the C2c2 of Doudna, Severinov, Chien, Shafiee, and Liu in order to have a system that can easily and safely be transported and used to diagnose bacterial or viral diseases in the field.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 3-5, 8, 11-12, and 32 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. 10,266,886.
Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘886 patent claims compositions for detecting the presence of nucleic acid target sequences using a Cas13 detection system, where the components of the ‘886 system are the same as the instant system. While the instant claims are directed to a diagnostic kit that can be lyophilized for point-of-care applications, it would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention that the composition of the ‘886 patent could be used in the diagnostic kit of the instant invention in a lyophilized form that provides for transport of the kit and use as a point-of-care application.
Claims 1, 3-5, 8, 11-12, and 32 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 10,266,887.
Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘887 patent claims methods for detecting the presence of nucleic acid target sequences using a Cas13 detection system, where the components of the ‘887 system are the same as the instant system. While the instant claims are directed to a diagnostic kit that can be lyophilized for point-of-care applications, it would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention that the composition of the ‘887 patent could be used in the diagnostic kit of the instant invention in a lyophilized form that provides for transport of the kit and use as a point-of-care application.
Claims 1, 3-5, 8, 11-12, and 32 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-28 of U.S. Patent No. 11,021,740.
Although the claims at issue are not identical, they are not patentably distinct from each other because both the ‘740 patent and the instant application claim diagnostic devices for use in methods for detecting the presence of nucleic acid target sequences using a Cas13 detection system having the same components. While the instant claims are directed to a diagnostic kit that can be lyophilized for point-of-care applications, it would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention that the composition of the ‘740 patent could be used in the diagnostic kit of the instant invention in a lyophilized form that provides for transport of the kit and use as a point-of-care application. Because both the ‘740 patent and the instant application claim devices for use in the same purpose and having the same components, the claims are not deemed to be patentably distinct.
Claims 1, 3-5, 8, 11-12, and 32 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-28 of U.S. Patent No. 11,104,937.
Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘937 patent claims systems for detecting the presence of nucleic acid target sequences using a Cas13 detection system, where the components of the ‘937 system are the same as the instant system. While the instant claims are directed to a diagnostic kit that can be lyophilized for point-of-care applications, it would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention that the composition of the ‘937 patent could be used in the diagnostic kit of the instant invention in a lyophilized form that provides for transport of the kit and use as a point-of-care application.
Claims 1, 3-5, 8, 11-12, and 32 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of U.S. Patent No. 11,174,515.
Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘515 patent claims systems for detecting the presence of nucleic acid target sequences using a Cas13 detection system, where the components of the ‘515 system are the same as the instant system. While the instant claims are directed to a diagnostic kit that can be lyophilized for point-of-care applications, it would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention that the composition of the ‘515 patent could be used in the diagnostic kit of the instant invention in a lyophilized form that provides for transport of the kit and use as a point-of-care application.
Claims 1, 3-4, 8, 11-12, and 32 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 11,453,907.
Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘907 patent claims methods for detecting the presence of nucleic acid target sequences using a Cas13 detection system, where the components of the ‘907 system are the same as the instant system. While the instant claims are directed to a diagnostic kit that can be lyophilized for point-of-care applications, it would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention that the composition of the ‘907 patent could be used in the diagnostic kit of the instant invention in a lyophilized form that provides for transport of the kit and use as a point-of-care application.
Claims 1, 3-5, 8, 11-12, and 32 are ejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 of U.S. Patent No. 11,618,928.
Although the claims at issue are not identical, they are not patentably distinct from each other because while the ‘928 patent claims a system for detecting the presence of nucleic acid target sequences where the components of the ‘928 system are the same as the instant system. While the instant claims are directed to a diagnostic kit that can be lyophilized for point-of-care applications, it would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention that the composition of the ‘928 patent could be used in the diagnostic kit of the instant invention in a lyophilized form that provides for transport of the kit and use as a point-of-care application.
Claims 1, 3-5, 8, 11-12, and 32 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 of U.S. Patent No. 11,633,732.
Although the claims at issue are not identical, they are not patentably distinct from each other because both the ‘732 patent and the instant application claim a diagnostic kit for detecting the presence of nucleic acid target sequences where the components of the ‘732 patent system are the same as the instant system. While the instant claims are directed to a diagnostic kit that can be lyophilized for point-of-care applications, it would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention that the composition of the ‘732 patent could be used in the diagnostic kit of the instant invention in a lyophilized form that provides for transport of the kit and use as a point-of-care application.
Claims 1, 3-5, 8, 11-12, and 32 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 11,851,702.
Although the claims at issue are not identical, they are not patentably distinct from each other because both the ‘702 patent and the instant application claim diagnostic devices for use in methods for detecting the presence of nucleic acid target sequences using a Cas13 detection system, where the components of the ‘702 system are the same as the instant system. While the instant claims are directed to a diagnostic kit that can be lyophilized for point-of-care applications, it would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention that the composition of the ‘702 patent could be used in the diagnostic kit of the instant invention in a lyophilized form that provides for transport of the kit and use as a point-of-care application.
Claims 1. 3-5, 8, 11-12, and 32 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-38 of U.S Patent No. 11,898,142.
Although the claims at issue are not identical, they are not patentably distinct from each other because both the ‘142 patent and the instant application claim a nucleic acid system comprising Cas protein(s), guide RNAs and detection (i.e., masking) construct. The ‘142 patent claims a system that includes amplification reagents, which may be isothermal amplification reagents thus claiming an amplicon. The ‘142 patent claims that the target sequence can be a DNA sequence and that the system can include an RNA polymerase and primer. The ’142 patent claims a device for the purpose of detecting the presence of a target nucleic acid., where the target nucleic acid is present in individual discrete volumes, which can be droplets that are defined on a substrate. The ‘142 patent claims that the substrate can be a paper or flexible polymer-based substrate. where the components of the ‘142 system are the same as the instant system. In addition, it would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention that the composition of the ‘142 patent could be used in the diagnostic kit of the instant invention in a lyophilized form that provides for transport of the kit and use as a point-of-care application.
Claims 1, 3-5, 8, 11-12, and 32 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 12,037,639.
Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘639 patent claims systems for detecting the presence of nucleic acid target sequences using a Cas13 detection system. While the instant claims are directed to a diagnostic kit, where the components of the ‘639 system are the same as the instant system. While the instant claims are directed to a diagnostic kit that can be lyophilized for point-of-care applications, it would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention that the composition of the ‘639 patent could be used in the diagnostic kit of the instant invention in a lyophilized form that provides for transport of the kit and use as a point-of-care application.
Claims 1, 3-5, 8, 11-12, and 32 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 12,203,145.
Although the claims at issue are not identical, they are not patentably distinct from each other because both the ‘145 patent and the instant application a claim nucleic acid detection system comprising Cas protein(s), guide RNAs and detection (i.e., masking) construct where the components of the ‘145 system are the same as the instant system. While the instant claims are directed to a diagnostic kit that can be lyophilized for point-of-care applications, it would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention that the composition of the ‘145 patent could be used in the diagnostic kit of the instant invention in a lyophilized form that provides for transport of the kit and use as a point-of-care application.
Claims 1, 3-5, 8, 11-12, and 32 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1,3, 5, 10, 29, 39, 47, 49-50, 71, 76, 129-133, and 141-168 of copending Application No. 16/955,380 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘380 application claims a method of detecting a viral target RNA and the instant application claims a nucleic acid diagnostic kit comprising Cas protein(s), guide RNAs and detection (i.e., masking) construct. The ‘380 application claims a system that includes amplification reagents, which may be isothermal amplification reagents thus claiming an amplicon. The ‘380 application claims that the target sequence can be a DNA sequence and that the system can include an RNA polymerase and primer. Because the ‘380 application claims a Cas protein that has the same structure as Cas13, it is deemed that this can encompass Cas13a, Cas13b, Cas13c, or Cas13d. The ‘380 application claims that the Cas13 comprises one or more HEPN domains, which have an RxxxxH motif sequence, as well as the possible amino acid residues. The components of the ‘380 application system are the same as the instant system. While the instant claims are directed to a diagnostic kit that can be lyophilized for point-of-care applications, it would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention that the composition of the ‘380 application could be used in the diagnostic kit of the instant invention in a lyophilized form that provides for transport of the kit and use as a point-of-care application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 3-5, 8, 11-12, and 32 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3- 5, 10, 12-13, 17, 19-20, 27-29, 39-40, and 43 of copending Application No. 16/961,820 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because both the ‘820 application and the instant application claim a nucleic acid system comprising Cas protein(s), guide RNAs and detection (i.e., masking) construct. The ‘820 application claims a system that includes amplification reagents, which may be isothermal amplification reagents thus claiming an amplicon. The ‘820 application claims that the target sequence can be a DNA sequence and that the system can include an RNA polymerase and primer. Because the ‘820 application claims a Cas protein that has the same structure as Cas13, it is deemed that this can encompass Cas13a, Cas13b, Cas13c, or Cas13d. The ‘820 application claims that the Cas13 comprises one or more HEPN domains, which have an RxxxxH motif sequence, as well as the possible amino acid residues. The ‘820 application claims a device for the purpose of detecting the presence of a target nucleic acid., where the target nucleic acid is present in individual discrete volumes, which can be droplets that are defined on a substrate. The ‘820 application claims that the substrate can be a paper or flexible polymer-based substrate. The components of the ‘820 application system are the same as the instant system. While the instant claims are directed to a diagnostic kit that can be lyophilized for point-of-care applications, it would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention that the composition of the ‘820 application could be used in the diagnostic kit of the instant invention in a lyophilized form that provides for transport of the kit and use as a point-of-care application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 3-5, 8, 11-12, and 32 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1, 11, 15, 24, 31, and 36-37 of copending Application No. 17/640,016 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because both the ‘016 application and the instant application claim a nucleic acid detection system comprising Cas protein(s), guide RNAs and detection (i.e., masking) construct, but does not claim a device for the purpose of detecting the presence of a target nucleic acid. The components of the ‘016 application system are the same as the instant system. While the instant claims are directed to a diagnostic kit that can be lyophilized for point-of-care applications, it would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention that the composition of the ‘016 application could be used in the diagnostic kit of the instant invention in a lyophilized form that provides for transport of the kit and use as a point-of-care application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 3-5, 8, 11-12, and 32 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 32, 38, and 47 of copending Application No. 18/268,156 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because both the ‘156 application and the instant application claim a nucleic acid detection system comprising Cas protein(s), guide RNAs and detection (i.e., masking) construct, but does not claim a device for the purpose of detecting the presence of a target nucleic acid. The components of the ‘156 application are the same as the instant system and further claim lyophilization of the CRISPR enzyme. While the instant claims are directed to a diagnostic kit that can be lyophilized for point-of-care applications, it would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention that the composition of the ‘156 application could be used in the diagnostic kit of the instant invention in a lyophilized form that provides for transport of the kit and use as a point-of-care application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 3-5, 8, 11-12, and 32 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 111-114 of copending Application No. 18/430,788 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because both the ‘788 application and the instant application claim a nucleic acid detection system comprising Cas protein(s), guide RNAs and detection (i.e., masking) construct, but does not claim a device for the purpose of detecting the presence of a target nucleic acid. The components of the ‘788 application are the same as the instant system. While the instant claims are directed to a diagnostic kit that can be lyophilized for point-of-care applications, it would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention that the composition of the ‘788 application could be used in the diagnostic kit of the instant invention in a lyophilized form that provides for transport of the kit and use as a point-of-care application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 3-5, 8, 11-12, and 32 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 9, 12-13, and 18-21 of copending Application No. 18/772,681 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because both the ‘681 application and the instant application claim a nucleic acid detection system comprising Cas protein(s), guide RNAs and detection (i.e., masking) construct, but does not claim a device for the purpose of detecting the presence of a target nucleic acid. The components of the ‘681 application are the same as the instant system. While the instant claims are directed to a diagnostic kit that can be lyophilized for point-of-care applications, it would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention that the composition of the ‘681 application could be used in the diagnostic kit of the instant invention in a lyophilized form that provides for transport of the kit and use as a point-of-care application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NANCY J LEITH whose telephone number is (313)446-4874. The examiner can normally be reached Monday - Thursday 8:00 AM - 6:30 PM.
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NANCY J. LEITH
Primary Examiner
Art Unit 1636
/NANCY J LEITH/Primary Examiner, Art Unit 1636