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
1. Applicant’s amendment and response filed 2/13/26 is acknowledged and has been entered.
2. The terminal disclaimer filed on 2/13/26 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration dates of US Patent Nos. 11,273,442 and 11,761,029 has been reviewed and is accepted. The terminal disclaimer has been recorded.
3. Applicant is reminded of Applicant's election with traverse of the species of cartridge consisting of first and second chambers connected without a third chamber in between, a programmable Cas12 nuclease, and a reporter comprising at least one deoxyribonucleotide in Applicant’s response filed 10/6/25.
Claims 97-117 are presently being examined. Instant claims 97 and 113 are independent claims.
4. The disclosure is objected to because of the following informalities: paragraph [0044] still refers to color drawings. Appropriate correction is required.
The Examiner acknowledges Applicant’s replacement drawings filed 2/13/26 and Applicant’s statement that none of the replacement figures are in color.
However, the specification at [0044] still discloses that the patent application file contains at least one drawing executed in color. Applicant is required to delete this paragraph and renumber the remaining paragraphs in the specification.
In addition, the specification at [0075] discloses “FIG.19A” with no other disclosure of other figures corresponding to Figure 19. There is only Figure 19 in the Drawings filed 2/13/26. Applicant is required to amend [0075] to disclose ‘FIG. 19’.
5. Applicant’s terminal disclaimer filed 2/13/26 has overcome the prior rejection of record of claims 97, 102-108, 111-113 and 115-117 as rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-34 of U.S. Patent No. 11,761,029.
6. Applicant’s terminal disclaimer filed 2/13/26 has overcome the prior rejection of record of claims 97-117 as rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-51 of U.S. Patent No. 11,273,442 (that issued from application serial no. 17/032,592).
7. 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.
8. The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
9. Claims 97, 99-114, 116 and 117 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by US 20220325363 A1 (IDS reference).
This rejection is necessitated by Applicant’s IDS with fee filed 2/13/26.
The applied reference has a common inventor and assignee with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2). This rejection under 35 U.S.C. 102(a)(2) might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C. 102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B) if the same invention is not being claimed; or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed in the reference and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement.
Instant base claim 97 recites:
“97. (New) A cartridge for detecting a target nucleic acid, the cartridge comprising:(a) a first chamber for receiving a sample comprising nucleic acids; and (b) a second chamber fluidically connected by a first valve to the first chamber; wherein: (i) the second chamber comprises a programmable nuclease, a guide nucleic acid, and a reporter; (ii) the programmable nuclease is effective to form an activated complex with the guide nucleic acid upon binding of the guide nucleic acid to the target nucleic acid; (iii) the reporter comprises a nucleic acid and a detection moiety; and (iv) the nucleic acid of the reporter is a cleavage substrate of the activated complex.”
Instant base claim 113 recites:
“113. (New) A method of detecting a target nucleic acid, the method comprising:(a) introducing a sample comprising the target nucleic acid into the first chamber of the cartridge of claim 97; (b) flowing the contents of the first chamber into the second chamber;(c) forming an activated complex comprising (i) the programmable nuclease, (ii) the guide nucleic acid, and (iii) the target nucleic acid or an amplicon thereof,(d) cleaving the reporter with the activated complex; and (e) detecting the detection moiety, thereby detecting the target nucleic acid.”
US 20220325363 A1 discloses systems and fluidic devices, including a cartridge device, for detection of target nucleic acids (e.g., abstract, [0004]). US 20220325363 A1 discloses that a sample chamber (i.e., a first chamber) is connected fluidically to a detection chamber (i.e., a second chamber comprising a programmable nuclease such as a CRISPER/Cas protein such as Cas12, Cas14, or Cas13, a guide nucleic acid, and a labeled detector nucleic acid, wherein the labeled detector nucleic acid is capable of being cleaved upon binding of the guide nucleic acid to a segment of a target nucleic acid; see below for further details), including wherein the detection reagent chamber is fluidically connected to the detection chamber (i.e., a detection region) via a resistance channel that is connected to a valve that can be a rotary, pneumatic, hydraulic or elastomeric valve, and in some embodiments, the valve is actuated by a solenoid or is controlled manually, magnetically, electrically, thermally, by a bistable circuit with a piezoelectric material, electrochemically with phase range, rheologically, pneumatically, with a check valve, capillarity, or any combination thereof. In some aspects, the rotary valve fluidically connects at least 3-5 chambers (e.g., [0004], [0005]). US 20220325363 A1 discloses examples of a valve disposed between the sample/amplification chamber and the reaction chamber that contains the programmable nuclease, guide nucleic acid, and reporter (e.g., Fig. 130A, depicting a solenoid valve, [0004], [0005]-the valve is a rotary (rotating), pneumatic, hydraulic, elastomeric, solenoid actuated valve, or is controlled manually, magnetically, electrically, thermally, phase change, rheologically, pneumatically or any combination thereof).
US 20220325363 A1 discloses that the detection reagent chamber of the cartridge comprises a programmable nuclease such as a CRISPER/Cas protein such as Cas12, Cas14, or Cas13, a guide nucleic acid, and a labeled detector nucleic acid, wherein the labeled detector nucleic acid is capable of being cleaved upon binding of the guide nucleic acid to a segment of a target nucleic acid (i.e., the detector nucleic acid is a reporter that comprises a nucleic acid and a detection moiety, wherein the nucleic acid of the reporter is a cleavage substrate of the activated complex (the activated complex being a complex of the programmable nuclease with the guide nucleic acid upon binding to the target nucleic acid) (e.g., [0004], [0025], [0026], [0029], [0037])). US 20220325363 A1 discloses that the labeled detector nucleic acid comprises in some aspects a single stranded reporter comprising a detection moiety, whereby the labeled detector produces a detectable signal upon cleavage of the detector nucleic acid ([0034]). US 20220325363 A1 discloses that the detector nucleic acids (i.e., reporter nucleic acids) can be DNA, RNA or a DNA/RNA hybrid (e.g., [0330]). US 20220325363 A1 discloses that the device may comprise multiple second chambers (reaction chambers comprising the programmable nuclease, guide nucleic acid, and a reporter, that the device may comprise a detection region, and that the support medium stabilizes the detectable signal (i.e., the reporter) generated by the cleaved detector molecule on the surface of the support medium (i.e., it is immobilized to the surface of the second or reaction chamber) (e.g., [0414], [0415]), including by through immobilization to a capture molecule (e.g., [0427], [0428]) .
US 20220325363 A1 discloses that in some aspects the microfluidic cartridge further comprises an amplification chamber comprising an amplification reagent, for example a polymerase, wherein the sample chamber is fluidically connected to the amplification chamber (i.e., a third chamber comprising a polymerase) (e.g., [0006], [0023]), i.e., the amplification chamber is disposed between the first or sample chamber and the second or detection chamber, and including wherein the amplification reagent is a polymerase (e.g., [0051]). US 20220325363 A1 discloses that the first chamber (sample chamber) may comprise a lysis buffer (e.g., [0007]) (i.e., the sample is lysed prior to flowing the contents of the sample chamber into the detection chamber). US 20220325363 A1 discloses that in some aspects the cartridge comprises 2 up to 10 detection chambers that are fluidically connected to the sample chamber (e.g., [0014], [0017]). US 20220325363 A1 discloses that a sliding valve may connect the amplification reagent chamber to the detection chamber (e.g., [0019]).
US 20220325363 A1 discloses a method for detecting a target nucleic acid comprising adding a sample from a subject to the microfluidic cartridge (i.e., to the sample chamber), correlating a detectable signal to the presence or absence of a target nucleic acid, and optionally quantifying the signal, thereby quantifying an amount of the target nucleic acid present in the sample ([0035], [0036]). US 20220325363 A1 discloses that in some aspects reporter is DNA, RNA, or a DNA/RNA hybrid (e.g., [0049] and [0330]) and may be conjugated to a substrate that can be a surface of the reaction chamber (e.g., [0046], [0047). US 20220325363 A1 discloses that in some aspects, the sample is lysed in the sample well, then moved from the sample chamber to an amplification chamber, then moved to a subsequent chamber via valve (e.g., [0160], [0161], [0379], [0395], [0462]). US 20220325363 A1 discloses that the sample can be dispensed into the sample chamber and flowed into a second chamber via a pneumatic valve, the second chamber being for example the amplification chamber comprising the polymerase or the detection chamber comprising the programmable nuclease, guide nucleic acid and reporter, wherein the sample may be lysed in the sample chamber ([0501]), and wherein after the sample is flowed to the reaction chamber, the activated complex cleaves the detector (or reporter) nucleic acid if the test nucleic acid is present in the sample, and the reacted sample and reagents are flowed along the support medium to a detection region, wherein the test nucleic acid may be detected (e.g., [0327]). From the disclosure in US 20220325363 A1, the order of steps for adding the sample comprising the target nucleic acid into the first (sample) chamber of the cartridge, flowing the contents of the sample chamber into the second chamber and therein forming an activated complex comprising the programmable nuclease mix comprising a programmable nuclease, the guide nucleic acid, and the target nucleic acid, optionally wherein the target nucleic acid is amplified before forming the activated complex, cleaving the reporter with the activated complex, and detecting the detection moiety, thereby detecting the target nucleic acid.
US 20220325363 A1 discloses a device configured to utilize the cartridge and measure fluorescence in the detection chamber of the cartridge (e.g., [0295])(i.e., the cartridge is in contact with a device comprising a detector configured to detect a signal of the detection moiety). See entire reference.
10. 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.
11. Claims 97-117 are rejected under 35 U.S.C. 103 as being obvious over
US 20220325363 A1 (IDS reference) in view of US 2017/0327867 A1 (IDS reference).
The applied reference has a common inventor and assignee with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2).
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
This rejection is necessitated by Applicant’s IDS with fee filed 2/13/26.
Instant base claim 97 recites:
“97. (New) A cartridge for detecting a target nucleic acid, the cartridge comprising:(a) a first chamber for receiving a sample comprising nucleic acids; and (b) a second chamber fluidically connected by a first valve to the first chamber; wherein: (i) the second chamber comprises a programmable nuclease, a guide nucleic acid, and a reporter; (ii) the programmable nuclease is effective to form an activated complex with the guide nucleic acid upon binding of the guide nucleic acid to the target nucleic acid; (iii) the reporter comprises a nucleic acid and a detection moiety; and (iv) the nucleic acid of the reporter is a cleavage substrate of the activated complex.”
Instant base claim 113 recites:
“113. (New) A method of detecting a target nucleic acid, the method comprising:(a) introducing a sample comprising the target nucleic acid into the first chamber of the cartridge of claim 97; (b) flowing the contents of the first chamber into the second chamber;(c) forming an activated complex comprising (i) the programmable nuclease, (ii) the guide nucleic acid, and (iii) the target nucleic acid or an amplicon thereof,(d) cleaving the reporter with the activated complex; and (e) detecting the detection moiety, thereby detecting the target nucleic acid.”
US 20220325363 A1 discloses systems and fluidic devices, including a cartridge device, for detection of target nucleic acids (e.g., abstract, [0004]). US 20220325363 A1 discloses that a sample chamber (i.e., a first chamber) is connected fluidically to a detection chamber (i.e., a second chamber comprising a programmable nuclease such as a CRISPER/Cas protein such as Cas12, Cas14, or Cas13, a guide nucleic acid, and a labeled detector nucleic acid, wherein the labeled detector nucleic acid is capable of being cleaved upon binding of the guide nucleic acid to a segment of a target nucleic acid; see below for further details), including wherein the detection reagent chamber is fluidically connected to the detection chamber (i.e., a detection region) via a resistance channel that is connected to a valve that can be a rotary, pneumatic, hydraulic or elastomeric valve, and in some embodiments, the valve is actuated by a solenoid or is controlled manually, magnetically, electrically, thermally, by a bistable circuit with a piezoelectric material, electrochemically with phase range, rheologically, pneumatically, with a check valve, capillarity, or any combination thereof. In some aspects, the rotary valve fluidically connects at least 3-5 chambers (e.g., [0004], [0005]). US 20220325363 A1 discloses examples of a valve disposed between the sample/amplification chamber and the reaction chamber that contains the programmable nuclease, guide nucleic acid, and reporter (e.g., Fig. 130A, depicting a solenoid valve, [0004], [0005]-the valve is a rotary (rotating), pneumatic, hydraulic, elastomeric, solenoid actuated valve, or is controlled manually, magnetically, electrically, thermally, phase change, rheologically, pneumatically or any combination thereof).
US 20220325363 A1 discloses that the detection reagent chamber of the cartridge comprises a programmable nuclease such as a CRISPER/Cas protein such as Cas12, Cas14, or Cas13, a guide nucleic acid, and a labeled detector nucleic acid, wherein the labeled detector nucleic acid is capable of being cleaved upon binding of the guide nucleic acid to a segment of a target nucleic acid (i.e., the detector nucleic acid is a reporter that comprises a nucleic acid and a detection moiety, wherein the nucleic acid of the reporter is a cleavage substrate of the activated complex (the activated complex being a complex of the programmable nuclease with the guide nucleic acid upon binding to the target nucleic acid) (e.g., [0004], [0025], [0026], [0029], [0037])). US 20220325363 A1 discloses that the labeled detector nucleic acid comprises in some aspects a single stranded reporter comprising a detection moiety, whereby the labeled detector produces a detectable signal upon cleavage of the detector nucleic acid ([0034]). US 20220325363 A1 discloses that the detector nucleic acids (i.e., reporter nucleic acids) can be DNA, RNA or a DNA/RNA hybrid (e.g., [0330]). US 20220325363 A1 discloses that the device may comprise multiple second chambers (reaction chambers comprising the programmable nuclease, guide nucleic acid, and a reporter, that the device may comprise a detection region, and that the support medium stabilizes the detectable signal (i.e., the reporter) generated by the cleaved detector molecule on the surface of the support medium (i.e., it is immobilized to the surface of the second or reaction chamber) (e.g., [0414], [0415]), including by through immobilization to a capture molecule (e.g., [0427], [0428]) .
US 20220325363 A1 discloses that in some aspects the microfluidic cartridge further comprises an amplification chamber comprising an amplification reagent, for example a polymerase, wherein the sample chamber is fluidically connected to the amplification chamber (i.e., a third chamber comprising a polymerase) (e.g., [0006], [0023]), i.e., the amplification chamber is disposed between the first or sample chamber and the second or detection chamber, and including wherein the amplification reagent is a polymerase (e.g., [0051]). US 20220325363 A1 discloses that the first chamber (sample chamber) may comprise a lysis buffer (e.g., [0007]) (i.e., the sample is lysed prior to flowing the contents of the sample chamber into the detection chamber). US 20220325363 A1 discloses that in some aspects the cartridge comprises 2 up to 10 detection chambers that are fluidically connected to the sample chamber (e.g., [0014], [0017]). US 20220325363 A1 discloses that a sliding valve may connect the amplification reagent chamber to the detection chamber (e.g., [0019]).
US 20220325363 A1 discloses a method for detecting a target nucleic acid comprising adding a sample from a subject to the microfluidic cartridge (i.e., to the sample chamber), correlating a detectable signal to the presence or absence of a target nucleic acid, and optionally quantifying the signal, thereby quantifying an amount of the target nucleic acid present in the sample ([0035], [0036]). US 20220325363 A1 discloses that in some aspects reporter is DNA, RNA, or a DNA/RNA hybrid (e.g., [0049] and [0330]) and may be conjugated to a substrate that can be a surface of the reaction chamber (e.g., [0046], [0047). US 20220325363 A1 discloses that in some aspects, the sample is lysed in the sample well, then moved from the sample chamber to an amplification chamber, then moved to a subsequent chamber via valve (e.g., [0160], [0161], [0379], [0395], [0462]). US 20220325363 A1 discloses that the sample can be dispensed into the sample chamber and flowed into a second chamber via a pneumatic valve, the second chamber being for example the amplification chamber comprising the polymerase or the detection chamber comprising the programmable nuclease, guide nucleic acid and reporter, wherein the sample may be lysed in the sample chamber ([0501]), and wherein after the sample is flowed to the reaction chamber, the activated complex cleaves the detector (or reporter) nucleic acid if the test nucleic acid is present in the sample, and the reacted sample and reagents are flowed along the support medium to a detection region, wherein the test nucleic acid may be detected (e.g., [0327]). From the disclosure in US 20220325363 A1, the order of steps for adding the sample comprising the target nucleic acid into the first (sample) chamber of the cartridge, flowing the contents of the sample chamber into the second chamber and therein forming an activated complex comprising the programmable nuclease mix comprising a programmable nuclease, the guide nucleic acid, and the target nucleic acid, optionally wherein the target nucleic acid is amplified before forming the activated complex, cleaving the reporter with the activated complex, and detecting the detection moiety, thereby detecting the target nucleic acid.
US 20220325363 A1 discloses a device configured to utilize the cartridge and measure fluorescence in the detection chamber of the cartridge (e.g., [0295])(i.e., the cartridge is in contact with a device comprising a detector configured to detect a signal of the detection moiety). See entire reference.
US 20220325363 A1 does not disclose wherein the second chamber (i.e., the reaction chamber comprising the programmable nuclease, guide nucleic acid, and reporter) further comprises a polymerase, including for amplifying the target nucleic acid in the second chamber (as is recited in instant dependent claims 98 and 115).
US 2017/0327867 A1 discloses a cartridge for detecting a target nucleic acid molecule in a sample comprising a first sample chamber that also further comprises a lysis reagent, and a reaction chamber. US 2017/0327867 A1 discloses placing valves for controlling fluid flow, wherein one or more valves can be used to selectively activate a specific port or vent and a pump or actuator can be used to drive fluid though the device. A further device comprises a detection system and a processing unit configured to perform an analysis of the output of the detection system. US 2017/0327867 A1 further discloses a method for detecting the presence of a target nucleic acid in a biological sample comprising adding the sample to a sample chamber, lysing the sample in the sample chamber, releasing the lysate into at least one reaction chamber, and performing the reaction to detect the target nucleic acid. US 2017/0327867 A1 also discloses amplifying the target nucleic acid in the reaction chamber, including via PCR i.e., polymerase chain reaction) (see entire reference, especially abstract, [0010]-[0012],[0016], [0017], [0019], [0026], [0101], [0105], [0109], [0234], Fig. 1).
It would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to have added a polymerase for PCR amplification to the reaction chamber as is disclosed by US 2017/0327867 A1.
One of ordinary skill in the art would have been motivated to do this, and with an expectation of success in doing so, in order to increase the signal for detection of the target nucleic acid molecule.
12. Claims 97, 99-101, 103, 107, 109-114 and 117 are rejected under 35 U.S.C. 103 as being unpatentable over US 20180340219 A1 (IDS reference) in view of US 20160186240 A1 (IDS reference).
This rejection is necessitated by Applicant’s IDS with fee filed 2/13/26.
Instant base claim 97 recites:
“97. (New) A cartridge for detecting a target nucleic acid, the cartridge comprising:(a) a first chamber for receiving a sample comprising nucleic acids; and (b) a second chamber fluidically connected by a first valve to the first chamber; wherein: (i) the second chamber comprises a programmable nuclease, a guide nucleic acid, and a reporter; (ii) the programmable nuclease is effective to form an activated complex with the guide nucleic acid upon binding of the guide nucleic acid to the target nucleic acid; (iii) the reporter comprises a nucleic acid and a detection moiety; and (iv) the nucleic acid of the reporter is a cleavage substrate of the activated complex.”
Instant base claim 113 recites:
“113. (New) A method of detecting a target nucleic acid, the method comprising:(a) introducing a sample comprising the target nucleic acid into the first chamber of the cartridge of claim 97; (b) flowing the contents of the first chamber into the second chamber;(c) forming an activated complex comprising (i) the programmable nuclease, (ii) the guide nucleic acid, and (iii) the target nucleic acid or an amplicon thereof,(d) cleaving the reporter with the activated complex; and (e) detecting the detection moiety, thereby detecting the target nucleic acid.”
Claim interpretation: As was stated in the last office action of record, the instant specification does not disclose a limiting definition for “cartridge”. Evidentiary reference Cambridge Dictionary (https://dictionary.cambridge.org/us/dictionary/english/cartridge, 2005, 1 page, of record) teaches that a cartridge is a small part with a particular purpose that can be easily replaced with another similar part. As was also stated in the prior office action of record, cartridges were known in the prior art prior to the filing date of the claimed invention for enclosing chambers and reagents for use in a fully automated system; for example, Xu et al. teach using a self-contained all-in-one cartridge for sample preparation and PCR for diagnosis of influenza (Lab Chip, 2010, 10: 3103-3111, of record). Also note that the specification does not disclose a limiting or other definition for the limitation “chamber”.
US 20180340219 A1 discloses a microfluidic device for detecting a target nucleic acid, wherein the device ([0155]) comprises valves, channels, and chambers, wherein the device may be connected to fluid flow actuators that allow directional movement of fluids within the device ([0284]), wherein the device comprises a plurality of individual discrete volumes (i.e., the inherent disclosure of a chamber or isolated space), each of which comprises a CRISPR effector protein (i.e., a programmable nuclease), one or more guide RNAs designed to bind to a corresponding target molecule, and a masking construct, and wherein is certain embodiments RNA amplification reagents may be preloaded into the individual discrete volumes or be added to the individual discrete volumes concurrently with or subsequent to addition of a sample to each individual discrete volume (e.g., [0025], [0248], [0155], [0005], [0006], and claim 1) (i.e., a programmable nuclease, guide nucleic acid, and reporter). The labeled detector nucleic acid is capable of being cleaved upon binding of the guide nucleic acid to a segment of a target nucleic acid (claims 1 and 7, masking construct deactivated by cleaving the masking construct so the detectable positive signal is unmasked) (i.e., the programmable nuclease is effective to form an activated complex with the guide nucleic acid upon binding of the guide nucleic acid to the target nucleic acid). The target nucleic acid is detected using a CRISPR programmable nuclease (e.g., [0181] disclosing RuvC catalytic CRISPR effector Cas 9 enzyme, and claim 6 that recites Cas13, and [0007]). The masking construct may comprise for example, a polynucleotide to which a detectable label and a masking component are attached (claim 8 at part e) (i.e., the reporter comprises a nucleic acid and a detection moiety and the nucleic acid of the reporter is a cleavage substrate of the activated complex). The reagent to amplify the target RNA or the target DNA comprises a polymerase (claims 14 and 15). In the device comprising one or more individual discrete volumes, the said volumes comprising a CRISPER system comprises one or more guide RNAs that are configured to bind to a different target molecule or molecules (claim 17). US 20180340219 A1 discloses a method for detecting target nucleic acids in samples comprising distributing a sample or set of samples into one or more said individual discrete volumes, amplification of one or more target molecules, incubating the sample or set of samples under conditions sufficient to allow binding of one or more guide RNAs to the one or more target molecules, activating the CRISPR effector protein via binding of the one or more guide RNAs to the one or more target molecules, wherein activating the CRISPR effector protein results in modification of the RNA-based masking construct such that a detectable positive signal is generated, and detecting said signal wherein detection indicates a presence of one or more target molecules in the sample (claim 22). The target molecule may be a target DNA (claim 23). US 20180340219 A1 discloses a flow cell, defined as a chamber comprising a solid surface across which one or more fluid reagents can be flowed ([0260]). US 20180340219 A1 discloses that devices of the invention may comprise inlet and outlet ports, or openings, which in turn may be connected to valves, tubes, channels, chambers, and syringes or pumps for the introduction and extraction of fluids, and the devices may be connected to fluid flow actuators that allow directional movement of fluids within the microfluidic device (e.g., [0284]). US 20180340219 A1 discloses that a cell lysis component for breaking open or lysing a cell for analysis of the material therein may be comprised in the individual reaction volume (e.g., [0253], an inherent teaching of lysing the sample when it is a cell in order to amplify the target nucleic acid therein). The order of the method for detecting a target RNA comprises distributing a sample comprising a target RNA(s) into one or more individual discrete volumes that comprise the CRISPR programmable nuclease, guide nucleic acid, and reporter (i.e, a plurality of second individual discrete volumes) under conditions sufficient to allow binding of the one or more target RNAs, activating the programmable nuclease via binding of the one or more guide RNAs to the one or more target molecules, wherein activating the programmable nuclease result in modification of the masking construct on the reporter such that a detectable positive signal is produced, and detecting the said positive signal, wherein detection of the detectable positive signal indicates a presence of one or more target molecules in the sample (e.g., [0025]), including wherein in some embodiments the sample RNA is amplified (e.g., [0027]). See entire reference.
US 20180340219 A1 does not disclose wherein the device is a cartridge, nor wherein a detection chamber is fluidically connected to a valve, and although it does disclose that a cell lysis component for breaking open or lysing a cell for analysis of the material therein may be comprised in the individual reaction volume, it does not explicitly disclose wherein the sample chamber also comprises one or more cell lysis reagents.
US 20160186240 A1 discloses that laboratory instrumentation for diagnostic testing is often purchased along with a regular supply of consumable tests or cartridges for high throughput processing (e.g., [0002], [0003]). US 20160186240 A1 discloses that a molecular diagnostic test device includes a housing, an amplification module and a detection module,12 wherein the amplification module receives the sample that is amplified via polymerase chain reaction, including lysis of the sample by reagents included in the system before amplification, and wherein the detection module is configured to receive an output from the amplification module and a reagent formulated to produce a signal that indicates the presence of the target amplicon within the input sample (e.g., abstract, [0248], [0250]-[0251], [0253]). US 20160186240 A1 discloses a molecular diagnostic fluidic device that comprises a detection chamber fluidically connected to a valve (Fig. 9, detection module 6800 connected to rotary (rotating) valve 6340), wherein the valve is connected to a sample metering channel (Fig. 9, rotary valve 6340 connected to sample prep module 6200 connected by fluidic path to meter the sample into the detection module); the detection reagent chamber is fluidically connection to the detection chamber via a resistance channel (Fig. 9, reagent storage module 6700 with chambers 6701-6704 connected to the detection chamber 6821-6825 by channel from reagent module to the channel 6812). The detection module 6800 in Fig. 9 is also the detection module 6800 in Figs. 46-49 ([0271]). US 20160186240 A1 discloses a sample chamber fluidically connected to the amplification reagent chamber (Fig. 9, 6200 connected to amplification module 6600) which is in turn fluidically connected to the amplification chamber (Fig. 9, [0224], 6200 connected to amplification module 6600 through mixing chamber 6500 having PCR (polymerase chain reaction) reagents). US 20160186240 A1 discloses a reagent port above the detection chamber (Fig. 9, 6700 reagent module with reagent port above 6800 detection chamber to deliver reagents to the detection module). US 20160186240 A1 discloses a pump (an actuator) to pump fluid from the amplification chamber to the detection chamber (Fig. 9, fluidic drive module 6400). US 20160186240 A1 discloses comprising two detection chambers ([0168], Fig. 49 at 6821-6825), as well as further comprising a sliding valve ([0198]). US 20160186240 A1 also discloses a manifold configured to accept the microfluidic cartridge, the manifold comprising a pump configured to pump fluid into the detection chamber (Fig. 9: fluidic drive module), a detector configured to detect a detectable signal produced by the labeled detector nucleic acid ([0499]: neofluorescence reader).
It would have been prima facie obvious to one of ordinary skill in the art before the filing date of the instant invention to have configured the device disclosed by the primary art reference as a cartridge as is disclosed by the secondary art reference, and with the chambers fluidically connected by valves, wherein an actuator is configured to move fluid from the sample chamber to the detection chamber, including via an intervening amplification chamber when present, and wherein a valve also fluidically connects the sample chamber with an amplification chamber in the alternate instance wherein the amplification reagents are disposed in a chamber in between the sample and detection chambers instead of in the sample chamber. It would have been prima facie obvious to one of ordinary skill in the art before the filing date of the instant invention to have placed a lysis reagent as disclosed by both references into the sample chamber. It would have been prima facie obvious to one of ordinary skill in the art before the filing date of the instant invention to have placed the individual discrete sample volume disclosed by the primary art reference in a sample chamber of the cartridge disclosed by the secondary art reference, followed by amplification of one or more target molecules by polymerase (either in the sample chamber or in an amplification chamber, the latter disclosed by the secondary art reference), incubating the amplified sample with the discrete reaction volume(s) in a reaction chamber or a plurality thereof to form an activated complex and to cleave the reporter with the activated complex, and to detect the reporter, thereby detecting the target nucleic acid when a detector such as taught by the secondary reference that is configured to detect a detectable signal produced by the reporter/label is used.
One of ordinary skill in the art would have been motivated to do this, and with a reasonable expectation of success in doing so, to produce disposable cartridges for high throughput analysis for detection of a target nucleic acid in a sample.
13. Claims 98 and 115 are rejected under 35 U.S.C. 103 as being unpatentable over US 20180340219 A1 (IDS reference) in view of US 20160186240 A1 (IDS reference) as applied to claims 97, 99-101, 103, 107, 109-114 and 117 above, and further in view of US 2017/0327867 A1 (IDS reference).
This rejection is necessitated by Applicant’s IDS with fee filed 2/13/26.
The disclosures and combination of US 20180340219 A1 in view of US 20160186240 A1 have been enunciated above, hereinafter referred to as the “combined references.”
The combined references do not disclose wherein the second chamber further comprises a polymerase (as is recited in instant dependent claims 98 and 115).
US 2017/0327867 A1 discloses a cartridge for detecting a target nucleic acid molecule in a sample comprising a first sample chamber that also further comprises a lysis reagent, and a reaction (second) chamber. US 2017/0327867 A1 discloses placing valves for controlling fluid flow, wherein one or more valves can be used to selectively activate a specific port or vent and a pump or actuator can be used to drive fluid though the device. A further device comprises a detection system and a processing unit configured to perform an analysis of the output of the detection system. US 2017/0327867 A1 further discloses a method for detecting the presence of a target nucleic acid in a biological sample comprising adding the sample to a sample chamber, lysing the sample in the sample chamber, releasing the lysate into at least one reaction chamber, and performing the reaction to detect the target nucleic acid. US 2017/0327867 A1 also discloses amplifying the target nucleic acid in the reaction chamber, including via PCR (see entire reference, especially abstract, [0010]-[0012],[0016], [0017], [0019], [0026], [0101], [0105], [0109], [0234], Fig. 1).
It would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to have added a polymerase for PCR amplification to the reaction chamber of the cartridge of the combined references as is disclosed by US 2017/0327867 A1.
One of ordinary skill in the art would have been motivated to do this, and with a reasonable expectation of success in doing so, in order to increase the signal for detection of the target nucleic acid molecule.
14. 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.
15. Upon further consideration, the prior rejection of record of claims 97, 98, 101, 102, 104, 106, 107, 109-111, 113 and 115-117 as provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14, 17, 18 and 72-29 of copending Application No. 18/393,023 is hereby withdrawn in view of the reporter being a downstream product of an enzyme-activated cleavage product of a second reporter by an enzyme rather than a cleavage substrate of the activated complex.
16. Court rulings have been quite clear that ONLY DIVISIONAL applications are entitled to the shield from double patenting under 35 USC 121. Indeed, in AMGEN INC v. HOFFMANN LA ROCHE LTD GMBH LA (Nos. 2009-1020, 2009-1096) the court discusses this issue at length and states:
Turning to the legislative history, the court observed that a House Report also referred specifically to “divisional application[s].” Id. Notably absent from the legislative history, in the court's view, was a suggestion “that the safe-harbor provision was, or needed to be, directed at anything but divisional applications.” Id. at 1361. From there, the court “conclude^] that the protection afforded by section 121 to applications (or patents issued therefrom) filed as a result of a restriction requirement is limited to divisional applications.” Id. at 1362. Accordingly, the court decided that the § 121 safe harbor did not apply to the patent before it, which issued from a continuation-in-part application. Id.
We are persuaded by the reasoning in Pfizer that the § 121 safe harbor provision does not protect continuation applications or patents descending from only continuation applications. The statute on its face applies only to divisional applications, and a continuation application, like a continuation-in-part application, is not a divisional application.
Given that Applicant chose to file the 18/541,650 case as a separate unrelated application, not as a DIV of the instant application, the instant rejection has been set forth.
Claims 97, 98, 100, 101, 105-107, 109, 111, 113 and 115-117 stand provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 63-75, 82-84, 92, 93, 99-101, 105 and 112 of copending Application No. 18/541,650.
The content of the claims of ‘650 are listed below in this rejection.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
With regard to the recitation in instant claim 117 of lysing the sample and instant claim 101 of a first chamber comprising one or more cell lysis reagents, note that claim 66 of ‘650 recites a sample preparation region further comprising a cellular digestion reagent (i.e., a cell lysis agent). With regard to instant claims 100 and 115, it would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to have comprised a polymerase for amplifying the target nucleic acid(s) prior to contacting with the programmable nuclease, guide nucleic acid and reporter in a third chamber in order to increase the amount of such target nucleic acid(s), particularly since the claims of ‘650 recite that the said ingredients form a complex that is activated upon binding the corresponding target nucleic acid or amplicon thereof (e.g., claim 84 of ‘650).
Claim 63 (and its dependent claims) of 18/541,650 recites a system for detecting a target nucleic acid, the system comprising:
a. an instrument;
b. a cartridge configured to interface with the instrument, the cartridge comprising:
i. a sample interface configured to receive a sample comprising one or more nucleic acids;
ii. one or more reagent capsules; and
iii. a detection region; a
c.guide nucleic acid disposed within the cartridge and that is complementary to the tar-get nucleic acid, or a portion thereof, of the one or more nucleic acids;
d. a programmable nuclease disposed within the cartridge and that is capable of being complexed with the guide nucleic acid that is complementary to the target nucleic acid, or a portion thereof, of the one or more nucleic acids, wherein the programmable nuclease is configured to be activated through binding of the guide nucleic acid to the target nucleic acid; and
a reporter disposed within the cartridge, the reporter comprising a cleavable nucleic acid and a detection moiety, wherein cleavage of the cleavable nucleic acid by the activated programmable nuclease releases the detection moiety from the cleavable nucleic acid, wherein the released detection moiety is configured to generate a signal; wherein the detection region is configured to detect the signal indicating the presence of the target nucleic acid.
Claim 112 of 18/541,650 is drawn to a cartridge for detecting a target nucleic acid, the cartridge comprising:
(a) a reagent reservoir;
(b) a programmable nuclease, wherein the programmable nuclease is configured to be activated through binding of a guide nucleic acid to a target nucleic acid;
(c) a reporter, the reporter comprising a cleavable nucleic acid and a detection moiety, wherein cleavage of the cleavable nucleic acid by the activated programmable nuclease releases the detection moiety from the cleavable nucleic acid, and wherein the released detection moiety is configured to generate a signal indicative of a presence of the target nucleic acid;
(d) a sample interface in fluid communication with the reagent reservoir, the sample interface configured to receive a sample;
(e) a detection region in fluid communication with the sample interface, the detection region comprising:
(i) a guide nucleic acid disposed within the detection region, wherein the guide nucleic acid is complementary to the target nucleic acid, or a portion thereof, of the one or more nucleic acids; and
(ii) a primer disposed within the detection region, wherein the primer is designed to amplify one or more nucleic acids in the sample; and
wherein the detection region is configured to amplify the one or more nucleic acids in the sample and to enable detection of the signal.
Claim 75 of 18/541,650 recites a system for multiplexed detection of a plurality of target nucleic acids comprising:
i. an instrument and
ii. a cartridge (comprising a sample interface, a sample preparation region, an amplification region and a detection region, each comprising a plurality of detection locations each comprising a reporter, a programmable nuclease complexed with a guide nucleic acid, wherein the reported and guide are immobilized to a surface of the detection region, wherein the programmable nuclease is configured to cleave the reporter and generate a different plurality of signals that indicate a presence of the target nucleic acid(s).
Claim 105 of 18/541,650 is drawn to a microfluidic device comprising:
a loading channel comprising a first capillary valve disposed upstream of a second capillary valve disposed therein;
a first chamber fluidically coupled to the loading channel upstream of the first capillary valve;
a second chamber fluidically coupled to the loading channel between the first capillary valve and the second capillary valve; and
a third chamber fluidically coupled to the loading channel downstream of the second capillary valve, wherein:
(a) each chamber of the first, second, and third chambers comprises an outlet;
(b) each of the first and second capillary valves have a cross-sectional area that is smaller than a cross-sectional area of the loading channel; and
(c) each outlet is gas-permeable and configured to retain liquid within the respective
chamber.
Claim 83 (and its dependent claims) of 18/541,650 recites a system comprising a microfluidic device comprising a plurality of chambers fluidically connected in sequence, wherein:
(a) each chamber of the plurality of chambers comprises a well, an inlet channel, an outlet, and a capillary valve;
(b) the capillary valve of each chamber (i) has a cross-sectional area that is smaller than a cross-sectional area of the inlet channel of the respective chamber, and (11) forms an entrance of the inlet channel of the next chamber in the sequence; and
(c) each outlet is air-permeable and configured to retain liquid within the respective chamber.
84. (Original) The system of claim 83, wherein each chamber further comprises detection reagents comprising a guide nucleic acid and a reporter, and further wherein:
(a) each guide nucleic acid (1) comprises a targeting sequence that hybridizes with a target nucleic acid of a plurality of different target nucleic acids or an amplicon thereof, and (2) is effective to form a complex with a programmable nuclease that is activated upon binding the corresponding target nucleic acid or amplicon thereof,
(b) the guide nucleic acid of a first chamber in the plurality of chambers comprises a different targeting sequence from the guide nucleic acid of a second chamber in the plurality of chambers; and
(c) each reporter (1) comprises a cleavable nucleic acid and a detection moiety, and (11) is configured to be cleaved to form a detectable cleavage product in response to activation of the complex in the well of the respective chamber.
The Examiner acknowledges Applicant’s remarks at section “B” in the amendment and response filed 2/13/26 that the rejection be held in abeyance until an otherwise allowable set of claims has been identified. The instant rejection is not the only outstanding rejection in the application.
17. Court rulings have been quite clear that ONLY DIVISIONAL applications are entitled to the shield from double patenting under 35 USC 121. Indeed, in AMGEN INC v. HOFFMANN LA ROCHE LTD GMBH LA (Nos. 2009-1020, 2009-1096) the court discusses this issue at length and states:
Turning to the legislative history, the court observed that a House Report also referred specifically to “divisional application[s].” Id. Notably absent from the legislative history, in the court's view, was a suggestion “that the safe-harbor provision was, or needed to be, directed at anything but divisional applications.” Id. at 1361. From there, the court “conclude^] that the protection afforded by section 121 to applications (or patents issued therefrom) filed as a result of a restriction requirement is limited to divisional applications.” Id. at 1362. Accordingly, the court decided that the § 121 safe harbor did not apply to the patent before it, which issued from a continuation-in-part application. Id.
We are persuaded by the reasoning in Pfizer that the § 121 safe harbor provision does not protect continuation applications or patents descending from only continuation applications. The statute on its face applies only to divisional applications, and a continuation application, like a continuation-in-part application, is not a divisional application.
Given that Applicant chose to file the 17/555,236 case as a separate unrelated application, not as a DIV of the instant application, the instant rejection has been set forth.
Claims 97, 99, 100-114, 116 and 117 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 4, 5, 10, 11, 21, 24, 28, 29, 38, 43, 47, 57, 63, 65, 71, 79, 84, 85, 94, 109, 122, 125, 142, 143,149 and 157 of copending Application No. 17/555,236 in view of US 20220325363 A1 and US 2017/0327867 A1 (IDS reference).
This rejection is necessitated by Applicant’s IDS with fee filed 2/13/26.
Applicant’s newly filed IDS references are US 20220325363 A1 and US 2017/0327867 A1. In addition, the publication of application serial no. 17/555,236 is Applicant’s newly filed IDS reference US 20220325363 A1.
Claims 1, 2, 4, 5, 10, 11, 21, 24, 28, 29, 38, 43, 47, 57, 63, 65, 71, 79, 94, 109, 122, 125, 142, 143 and 149 of 17/555,236 are drawn to a microfluidic cartridge comprising an amplification chamber fluidically connected to a valve, a detection chamber fluidically connected to the valve, and a detection reagent chamber fluidically connected to the detection chamber via a resistance channel, the detection reagent chamber comprising a programmable nuclease, a guide nucleic acid, and a labeled detector nucleic acid, wherein the labeled detector nucleic acid is capable of being cleaved upon binding of the guide nucleic acid to a segment of a target nucleic acid. The valve may be a rotary, pneumatic, hydraulic or elastomeric valve, and it may be actuated (by an actuator) by a solenoid or controlled manually, magnetically, electrically, thermally, by a bistable circuit, with a piezoelectric material, electrochemically, with phase change, rheologically, pneumatically, with a check valve with capillarity, or a combination thereof. The cartridge may also comprise one or more of a sample chamber fluidically connected to an amplification reagent chamber, a lysis buffer storage chamber fluidically connected to a sample chamber that is fluidically connected to the amplification reagent chamber with a valve between the two, and a second valve fluidically connected to the detection reagent chamber and the detection chamber. The programmable nuclease may be a Cas12, Cas13, or a Cas14.
Claims 84 and 85 of 17/555,236 are drawn to a manifold configured to accept the microfluidic cartridge of claim 1, comprising a pump to pump fluid into the detection chamber, an illumination source configured to illuminate the detection chamber, a detector configured to detect a detectable signal produced by the labeled detector nucleic acid, and a heater configured to heat the amplification chamber.
Claim 157 of 17/555,236 is drawn to a method of detecting a target nucleic acid comprising providing a sample from a subject, adding the sample to the cartridge, detecting a detectable signal produced by a cleavage product of the labeled detector nucleic acid in response to the presence of a target nucleic acid, and optionally quantifying the detectable signal, thereby quantifying an amount of the target nucleic acid present in the sample.
The method claim of 17/555,236 does not recite forming an activated complex, nor a step for lysing the sample prior to flowing the contents of the first (or sample) chamber into the second (or reaction) chamber. The claims of 17/555,236 do not recite that the labeled detector nucleic acid is a reporter that is immobilized to a surface within the second chamber, nor that the reporter is a hybrid reporter comprising at least one ribonucleotide and at least one deoxyribonucleotide, nor that the amplification chamber comprises a polymerase, nor that the cartridge comprises a detection region fluidically connected to the second chamber, nor wherein the cartridge comprises a plurality of second chambers, nor that the target nucleic acid is amplified in the second chamber, nor wherein the sample is lysed, including by a cell lysis agent comprised in the first (sample) chamber(although it does recite a lysis agent storage chamber fluidically connected to the sample chamber), nor wherein the second chamber further comprises a polymerase, including for amplifying the target nucleic acid in the second chamber, nor does
US 20220325363 A1 discloses systems and fluidic devices, including a cartridge device, for detection of target nucleic acids (e.g., abstract, [0004]). US 20220325363 A1 discloses that a sample chamber (i.e., a first chamber) is connected fluidically to a detection chamber (i.e., a second chamber comprising a programmable nuclease such as a CRISPER/Cas protein such as Cas12, Cas14, or Cas13, a guide nucleic acid, and a labeled detector nucleic acid, wherein the labeled detector nucleic acid is capable of being cleaved upon binding of the guide nucleic acid to a segment of a target nucleic acid; see below for further details), including wherein the detection reagent chamber is fluidically connected to the detection chamber (i.e., a detection region) via a resistance channel that is connected to a valve that can be a rotary, pneumatic, hydraulic or elastomeric valve, and in some embodiments, the valve is actuated by a solenoid or is controlled manually, magnetically, electrically, thermally, by a bistable circuit with a piezoelectric material, electrochemically with phase range, rheologically, pneumatically, with a check valve, capillarity, or any combination thereof. In some aspects, the rotary valve fluidically connects at least 3-5 chambers (e.g., [0004], [0005]). US 20220325363 A1 discloses that the system may further comprise a second guide nucleic acid, programmable DNA nuclease and guide nucleic acid (e.g., [0049]). US 20220325363 A1 discloses that the detection reagent chamber of the cartridge comprises a programmable nuclease such as a CRISPER/Cas protein such as Cas12, Cas14, or Cas13, a guide nucleic acid, and a labeled detector nucleic acid, wherein the labeled detector nucleic acid is capable of being cleaved upon binding of the guide nucleic acid to a segment of a target nucleic acid (i.e., the detector nucleic acid is a reporter that comprises a nucleic acid and a detection moiety, wherein the nucleic acid of the reporter is a cleavage substrate of the activated complex (the activated complex being a complex of the programmable nuclease with the guide nucleic acid upon binding to the target nucleic acid) (e.g., [0004], [0025], [0026], [0029], [0037])). US 20220325363 A1 discloses that the labeled detector nucleic acid comprises in some aspects a single stranded reporter comprising a detection moiety, whereby the labeled detector produces a detectable signal upon cleavage of the detector nucleic acid ([0034]). US 20220325363 A1 discloses that the detector nucleic acids can be DNA, RNA or a DNA/RNA hybrid (e.g., [0330]). US 20220325363 A1 discloses that in some aspects the microfluidic cartridge further comprises an amplification chamber comprising an amplification reagent, for example a polymerase, wherein the sample chamber is fluidically connected to the amplification chamber (i.e., a third chamber comprising a polymerase) (e.g., [0006], [0023]), i.e., the amplification chamber is disposed between the first or sample chamber and the second or detection chamber, and including wherein the amplification reagent is a polymerase (e.g., [0051]). US 20220325363 A1 discloses that the first chamber (sample chamber) may comprise a lysis buffer (e.g., [0007]) (i.e., the sample is lysed prior to flowing the contents of the sample chamber into the detection chamber). US 20220325363 A1 discloses that in some aspects the cartridge comprises 2 up to 10 detection chambers that are fluidically connected to the sample chamber (e.g., [0014], [0017]). US 20220325363 A1 discloses that a sliding valve may connect the amplification reagent chamber to the detection chamber (e.g., [0019]). US 20220325363 A1 discloses a method for detecting a target nucleic acid comprising adding a sample from a subject to the microfluidic cartridge, correlating a detectable signal to the presence or absence of a target nucleic acid, and optionally quantifying the signal, thereby quantifying an amount of the target nucleic acid present in the sample ([0035]). US 20220325363 A1 discloses that in some aspects the reporter is DNA, RNA, or a DNA/RNA hybrid (e.g., [0049] and [0330]) and may be conjugated to a substrate that can be a surface of the reaction chamber (e.g., [0046], [0047). US 20220325363 A1 discloses a device configured to utilize the cartridge and measure fluorescence in the detection chamber of the cartridge (e.g., [0295])(i.e., the cartridge is in contact with a device comprising a detector configured to detect a signal of the detection moiety). The order of steps for adding the sample comprising the target nucleic acid into the first (sample) chamber of the cartridge, flowing the contents of the sample chamber into the second chamber and therein forming an activated complex comprising the programmable nuclease mix comprising a programmable nuclease, the guide nucleic acid, and the target nucleic acid, optionally wherein the target nucleic acid if amplified before forming the activated complex, cleaving the reporter with the activated complex, and detecting the detection moiety, thereby detecting the target nucleic acid. See entire reference.
US 2017/0327867 A1 discloses a cartridge for detecting a target nucleic acid molecule in a sample comprising a first sample chamber that also further comprises a lysis reagent, and a reaction chamber. US 2017/0327867 A1 discloses placing valves for controlling fluid flow, wherein one or more valves can be used to selectively activate a specific port or vent and a pump or actuator can be used to drive fluid though the device. A further device comprises a detection system and a processing unit configured to perform an analysis of the output of the detection system. US 2017/0327867 A1 further discloses a method for detecting the presence of a target nucleic acid in a biological sample comprising adding the sample to a sample chamber, lysing the sample in the sample chamber, releasing the lysate into at least one reaction chamber, and performing the reaction to detect the target nucleic acid. US 2017/0327867 A1 also discloses amplifying the target nucleic acid in the reaction chamber, including via PCR (see entire reference, especially abstract, [0010]-[0012],[0016], [0017], [0019], [0026], [0101], [0105], [0109], [0234], Fig. 1).
It would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to have immobilized the labeled detector nucleic acid to a surface of within the second chamber (a detection region), the detector nucleic acid being a reporter that comprises a nucleic acid and a detection moiety, as is disclosed by US 20220325363 A1, to have used a hybrid reporter comprising at least one ribonucleotide and at least one deoxyribonucleotide as is disclosed by US 20220325363 A1, to have lysed the sample using a cell lysis agent comprised in the first chamber (sample chamber) as is disclosed by US 20220325363 A1 or to have lysed it prior to the flowing step, to have comprised a polymerase in the amplification chamber as is disclosed by US 20220325363 A1 or to have comprised it in the reaction chamber and amplified it therein by PCR as is disclosed by US 2017/0327867 A1. (US 20220325363 A1 teaches that the activated complex is a complex of the programmable nuclease with the guide nucleic acid upon binding to the target nucleic acid.)
One of ordinary skill in the art would have been motivated to do this, and with a reasonable expectation of success in doing so, in order to configure the cartridge with a detector region, and to have used any suitable reporter, and to have lysed a cell sample prior to analyzing the sample for a target nucleic acid comprised within the cells. One of ordinary skill in the art would have been motivated to have comprised the polymerase in the amplification chamber as is disclosed by US 20220325363 A1 or to have comprised it in the reaction chamber and amplified it therein by PCR as is disclosed by US 2017/0327867 A1, and with a reasonable expectation of success in doing so, in order to amplify the target nucleic acid for better detection.
It would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to have configured the cartridge of the claims of ‘236 to comprise a plurality of second chambers.
One of ordinary skill in the art would have been motivated to do this, and with a reasonable expectation of success in doing so, because in light of the disclosure of US 20220325363 A1 that the system may further comprise a second guide nucleic acid, programmable DNA nuclease and guide nucleic acid, one of ordinary skill in the art could detect more than one target nucleic acid sequence by doing so.
It would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to have flowed the contents of the sample chamber to that of the reaction chamber, thereby forming an activated complex.
One of ordinary skill in the art would have been motivated to do this, and with a reasonable expectation of success in doing so because the cartridge is configured with the reagents to do so.
18. Court rulings have been quite clear that ONLY DIVISIONAL applications are entitled to the shield from double patenting under 35 USC 121. Indeed, in AMGEN INC v. HOFFMANN LA ROCHE LTD GMBH LA (Nos. 2009-1020, 2009-1096) the court discusses this issue at length and states:
Turning to the legislative history, the court observed that a House Report also referred specifically to “divisional application[s].” Id. Notably absent from the legislative history, in the court's view, was a suggestion “that the safe-harbor provision was, or needed to be, directed at anything but divisional applications.” Id. at 1361. From there, the court “conclude^] that the protection afforded by section 121 to applications (or patents issued therefrom) filed as a result of a restriction requirement is limited to divisional applications.” Id. at 1362. Accordingly, the court decided that the § 121 safe harbor did not apply to the patent before it, which issued from a continuation-in-part application. Id.
We are persuaded by the reasoning in Pfizer that the § 121 safe harbor provision does not protect continuation applications or patents descending from only continuation applications. The statute on its face applies only to divisional applications, and a continuation application, like a continuation-in-part application, is not a divisional application.
Given that Applicant chose to file the 17/938,640 case as a separate unrelated application, not as a DIV of the instant application, the instant rejection has been set forth.
Claims 97, 99, 100-114, 116 and 117 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13, 15, 27 and 29-33 of copending Application No. 17/938,640 in view of US 20220325363 A1 (IDS reference) and US 2017/0327867 A1 (IDS reference).
This rejection is necessitated by Applicant’s IDS with fee filed 2/13/26.
Claims 1-13, 15, 27, 29 and 30 of 17/938,640 are drawn to a composition comprising a programmable nuclease, a pool of guide nucleic acids, and a detector nucleic acid that comprises a detection moiety that produces a detectable signal responsive to cleavage by the programmable nuclease upon formation of a complex comprising the programmable nuclease upon formation of a complex comprising the programmable nuclease, the at least one guide nucleic acid and the segment of the target nucleic acid (base claim 1), wherein the programmable nuclease is a type V or VI CRISPR-Cas enzyme (claim 15), wherein the target nucleic acid is DNA or RNA (claim 27).
Claims 31-33 of 17/938,640 are drawn to a method of assaying for a segment of a target nucleic acid in a sample comprising contacting the sample to the said composition and assaying for a detectable signal, including further comprising amplifying the target nucleic acid.
The claims of 17/938,640 do not recite that the composition is contained in a second chamber of a cartridge that is fluidically connected by a first valve to a first chamber for receiving a target nucleic acid sample (as is recited in instant base claims 97 and 113), nor that the first chamber comprises one or more cell lysis reagents (instant claim 101), the programmable Cas nucleases are Cas12, Cas13 or Cas14 (instant claims 102-104), the cartridge comprises a detection region fluidically connected to the second chamber (instant claim 105), the reporter is immobilized to a surface within the second chamber (instant claim 106), the reporter comprises at least one ribonucleotide or at least one deoxyribonucleotide (instant claim 107) or a hybrid thereof (instant claim 108), the cartridge is in contact with a device comprising an actuator configure to move fluid from the first to the second chamber (instant claim 110), the cartridge is in contact with a device comprising a detector configured to detect a signal of the detection moiety (claim 111), the first valve comprises one of the recited elements in instant claim 112 (such as a sliding, rotating, or pneumatic valve), nor amplification with a polymerase in the second or third chamber, nor the steps recited in the method of detecting a target nucleic acid recited in instant base claim 113 and its dependent claims.
US 20220325363 A1 discloses systems and fluidic devices, including a cartridge device, for detection of target nucleic acids (e.g., abstract, [0004]). US 20220325363 A1 discloses that a sample chamber (i.e., a first chamber) is connected fluidically to a detection chamber (i.e., a second chamber comprising a programmable nuclease such as a CRISPER/Cas protein such as Cas12, Cas14, or Cas13, a guide nucleic acid, and a labeled detector nucleic acid, wherein the labeled detector nucleic acid is capable of being cleaved upon binding of the guide nucleic acid to a segment of a target nucleic acid; see below for further details), including wherein the detection reagent chamber is fluidically connected to the detection chamber (i.e., a detection region) via a resistance channel that is connected to a valve that can be a rotary, pneumatic, hydraulic or elastomeric valve, and in some embodiments, the valve is actuated by a solenoid or is controlled manually, magnetically, electrically, thermally, by a bistable circuit with a piezoelectric material, electrochemically with phase range, rheologically, pneumatically, with a check valve, capillarity, or any combination thereof. In some aspects, the rotary valve fluidically connects at least 3-5 chambers (e.g., [0004], [0005]). US 20220325363 A1 discloses that the system may further comprise a second guide nucleic acid, programmable DNA nuclease and guide nucleic acid (e.g., [0049]). US 20220325363 A1 discloses that the detection reagent chamber of the cartridge comprises a programmable nuclease such as a CRISPER/Cas protein such as Cas12, Cas14, or Cas13, a guide nucleic acid, and a labeled detector nucleic acid, wherein the labeled detector nucleic acid is capable of being cleaved upon binding of the guide nucleic acid to a segment of a target nucleic acid (i.e., the detector nucleic acid is a reporter that comprises a nucleic acid and a detection moiety, wherein the nucleic acid of the reporter is a cleavage substrate of the activated complex (the activated complex being a complex of the programmable nuclease with the guide nucleic acid upon binding to the target nucleic acid) (e.g., [0004], [0025], [0026], [0029], [0037])). US 20220325363 A1 discloses that the labeled detector nucleic acid comprises in some aspects a single stranded reporter comprising a detection moiety, whereby the labeled detector produces a detectable signal upon cleavage of the detector nucleic acid ([0034]). US 20220325363 A1 discloses that the labeled detector nucleic acids can be DNA, RNA or a DNA/RNA hybrid (e.g., [0330]). US 20220325363 A1 discloses that in some aspects the microfluidic cartridge further comprises an amplification chamber comprising an amplification reagent, for example a polymerase, wherein the sample chamber is fluidically connected to the amplification chamber (i.e., a third chamber comprising a polymerase) (e.g., [0006], [0023]), i.e., the amplification chamber is disposed between the first or sample chamber and the second or detection chamber, and including wherein the amplification reagent is a polymerase (e.g., [0051]). US 20220325363 A1 discloses that the first chamber (sample chamber) may comprise a lysis buffer (e.g., [0007]) (i.e., the sample is lysed prior to flowing the contents of the sample chamber into the detection chamber). US 20220325363 A1 discloses that in some aspects the cartridge comprises 2 up to 10 detection chambers that are fluidically connected to the sample chamber (e.g., [0014], [0017]). US 20220325363 A1 discloses that a sliding valve may connect the amplification reagent chamber to the detection chamber (e.g., [0019]). US 20220325363 A1 discloses a method for detecting a target nucleic acid comprising adding a sample from a subject to the microfluidic cartridge, correlating a detectable signal to the presence or absence of a target nucleic acid, and optionally quantifying the signal, thereby quantifying an amount of the target nucleic acid present in the sample ([0035]). US 20220325363 A1 discloses that in some aspects the reporter is DNA, RNA, or a DNA/RNA hybrid (e.g., [0049] and [0330]) and may be conjugated to a substrate that can be a surface of the reaction chamber (e.g., [0046], [0047). US 20220325363 A1 discloses a device configured to utilize the cartridge and measure fluorescence in the detection chamber of the cartridge (e.g., [0295])(i.e., the cartridge is in contact with a device comprising a detector configured to detect a signal of the detection moiety). The order of steps for adding the sample comprising the target nucleic acid into the first (sample) chamber of the cartridge, flowing the contents of the sample chamber into the second chamber and therein forming an activated complex comprising the programmable nuclease mix comprising a programmable nuclease, the guide nucleic acid, and the target nucleic acid, optionally wherein the target nucleic acid if amplified before forming the activated complex, cleaving the reporter with the activated complex, and detecting the detection moiety, thereby detecting the target nucleic acid. See entire reference.
US 2017/0327867 A1 discloses a cartridge for detecting a target nucleic acid molecule in a sample comprising a first sample chamber that also further comprises a lysis reagent, and a reaction chamber. US 2017/0327867 A1 discloses placing valves for controlling fluid flow, wherein one or more valves can be used to selectively activate a specific port or vent and a pump or actuator can be used to drive fluid though the device. A further device comprises a detection system and a processing unit configured to perform an analysis of the output of the detection system. US 2017/0327867 A1 further discloses a method for detecting the presence of a target nucleic acid in a biological sample comprising adding the sample to a sample chamber, lysing the sample in the sample chamber, releasing the lysate into at least one reaction chamber, and performing the reaction to detect the target nucleic acid. US 2017/0327867 A1 also discloses amplifying the target nucleic acid in the reaction chamber, including via PCR (see entire reference, especially abstract, [0010]-[0012],[0016], [0017], [0019], [0026], [0101], [0105], [0109], [0234], Fig. 1). US 2017/0327867 A1 further discloses a method for detecting the presence of a target nucleic acid in a biological sample comprising adding the sample to a sample chamber, lysing the sample in the sample chamber, releasing the lysate into at least one reaction chamber, and performing the reaction to detect the target nucleic acid. US 2017/0327867 A1 also discloses amplifying the target nucleic acid in the reaction chamber, including via PCR (see entire reference, especially abstract, [0010]-[0012],[0016], [0017], [0019], [0026], [0101], [0105], [0109], [0234], Fig. 1).
It would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to have placed the composition recited in the claims of 17/398,640 into a second chamber of a cartridge, with a target sample disposed in a first chamber of the cartridge fluidically connected to the second chamber via a valve such as a rotary (rotating), sliding, or pneumatic valve, wherein the first chamber comprises one or more cell lysis reagents and the CAS nuclease is one of Cas12, Cas13, or Cas 14, the detector nucleic acid is RNA, DNA or an RNA/DNA hybrid, as is disclosed by US 20220325363 A1. It would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to have immobilized the reporter (detector) to a surface within the second chamber as US 20220325363 A1 discloses it may be conjugated to a substrate that can be a surface of the reaction chamber as well as to configure the cartridge to comprise a detection region fluidically connected to the second chamber as is also disclosed by US 20220325363 A1. In addition US 2017/0327867 A1 discloses a cartridge with a sample chamber including a lysis buffer to lyse the sample in the sample chamber, releasing the lysed sample into at least one reaction chamber, and performing the reaction to detect the target nucleic acid.
One of ordinary skill in the art would have been motivated to do this, and with a reasonable expectation of success in doing so, because the claims of 17/938,640 do not provide any device for using the composition comprising a programmable nuclease, guide nuclease and detector nucleic acid, including in the claims directed to a method for assaying for a target nucleic acid in a sample, while US 20220325363 A1 provides a cartridge comprising chambers that are fluidically connected to comprise the sample and said composition to effect the containment, mixing, reaction of the sample and composition. Cartridges were known in the art prior to the filing date of the claimed invention for enclosing chambers and reagents for use in a fully automated system, and US 20220325363 A1 discloses cartridges as well as automated systems. In addition, Xu et al., for example, teach using a self-contained all-in-one cartridge for sample preparation and PCR for diagnosis of influenza (Lab Chip, 2010, 10: 3103-3111, of record).
It would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to have amplified the target nucleic acid using polymerase in either a third chamber of the cartridge disposed between the sample chamber and the reaction chamber as is disclosed by US 20220325363 A1 or to have amplified it in the reaction chamber as disclosed by US 2017/0327867 A1.
One of ordinary skill in the art would have been motivated to do this, and with a reasonable expectation of success in doing so, in order to increase the target nucleic acid for better signal detection.
It would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to have placed the cartridge in contact with a device comprising an actuator configure to move fluid from the first to the second chamber and/or to have used pumps, and to have placed the cartridge is in contact with a device comprising a detector configured to detect a signal of the detection moiety, as US 2017/0327867 A1 discloses a pump or actuator can be used to drive fluid though the cartridge device.
One of ordinary skill in the art would have been motivated to do this, and with a reasonable expectation of success in doing so, because the claims of 17/938,640 do not provide for the cartridge system or a means such as an actuator or pump to move fluid between chambers.
It would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to have comprised a detection system with the cartridge device.
One of ordinary skill in the art would have been motivated to do this, and with a reasonable expectation of success in doing so, because the claims of 17/938,640 recite a detector nucleic acid and assaying for the detectable signal, but do not recite the means to do so, while the art reference US 2017/0327867 A1 discloses that the device may comprise a detection system and a processing unit configured to perform an analysis of the output of the detection system.
As regards the method of assaying for a segment of a target nucleic acid in a sample comprising contacting the sample to the composition and assaying for the detectable signal, and a step of amplifying the target nucleic acid (either in the first or second chamber as is alternatively disclosed by US 20220325363 A1 or US 2017/0327867 A1, respectively), it would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to have flowed the contents of the first (sample) chamber into the second (reaction) chamber (comprising the programmable nuclease, guide, nuclease, and detectable reporter nucleic acid) whereby the mixing starts the formation of an activated complex comprising the programmable nuclease, the guide nucleic acid and the target nucleic acid or an amplicon thereof (that was formed using a polymerase for amplification), and whereby the reporter is cleaved by the activated complex, and detecting a detection moiety (the claims of 17/938,640 recite a “detector” nucleic acid, so it would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to have performed these steps using the cartridge form of the composition of the claims of 17/938,640 as modified by the art references), wherein the contents of the second chamber are flowed into a detection region of the cartridge prior to the detecting step as is disclosed by US 20220325363 A1. One of ordinary skill in the art would have been motivated to do this, and with a reasonable expectation of success in doing so, in order to use the composition for the aim of the method recited in the claims of 17/938,640 of assaying for a segment of a target nucleic acid in a sample, particularly in light of the disclosure of US 2017/0327867 A1 of a method for detecting the presence of a target nucleic acid in a biological sample comprising adding the sample to a sample chamber, lysing the sample in the sample chamber, releasing the lysate into at least one reaction chamber, and performing the reaction to detect the target nucleic acid.
19. No claim is allowed.
20. Applicant's submission of an information disclosure statement under 37 CFR 1.97(c) with the timing fee set forth in 37 CFR 1.17(p) on 2/13/26 prompted the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 609.04(b). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
21. Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARIANNE DIBRINO whose telephone number is (571)272-0842. The examiner can normally be reached on M, T, Th, F.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the Examiner’s supervisor, MISOOK YU can be reached on 571-272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/Marianne DiBrino/
Marianne DiBrino, Ph.D.
Patent Examiner
Group 1640
Technology Center 1600
/MISOOK YU/Supervisory Patent Examiner, Art Unit 1641
Prosecution Insights