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 .
Applicant’s preliminary amendment filed on April 28, 2022 is acknowledged. Claims 1, 2, 7-9, 11, 19-21, 41, 77, 94-96, 98, 100, 102, and 104-109 are pending and under examination in this Office action
Information Disclosure Statement
The information disclosure statement (IDS) submitted on July 27, 2022 has been considered by the examiner.
Claim Rejections - 35 USC § 102
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)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention.
(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.
Claims 1, 2, 7, 9, 11, 19-20, 41, 77, 94-96, 98, 100, 102, and 104-109 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Gootenberg et al. (US Patent Application Publication US 2023/0127948).
Gootenberg et al., discloses methods for determining the presence of viral, SARS-CoV-2 and bacterial nucleic acids in a sample, the method comprising contacting the sample with a CRISPR/Cas complex comprising an effector nuclease and a guide RNA encoding a nucleic acid that hybridizes to a target nucleic acid, Cas12 nuclease, wherein the one or more nucleases is not the same as the effector nuclease, one or more oligonucleotides, and a fluorescence reporter, and measuring a fluorescence signal emitted from the fluorescence reporter, wherein a presence of the fluorescence signal indicates the presence of the target nucleic acid in the sample (see paragraphs [0026-0029], [0084-0096], [0318], [0392-0396], Figures 1-64).
Regarding present claim 41, Gootenberg et al., discloses a kit (see paragraph [0114])
Regarding present claim 2, Gootenberg discloses CRISPR/Cas complex exhibiting collateral cleavage activity (see paragraph [0584]).
Regarding present claim 11, Gootenberg discloses a sequence of an effector nuclease Cas12 comprising a sequence identical with present SEQ ID NO: 6 (see SEQ ID NO: 4 in Gootenburg and the sequence alignment below).
Regarding present claims 96 and 107, Gootenberg discloses SARS-CoV-2, Papillomavirus, Herpesvirus and more (see paragraph [0440].
Regarding present claim 98, Gootenberg discloses Staphylococcus aureus, Acinetobacter baumannii, Enterobacter cloacae, Enterococcus faecalis, Enterococcus faecium, Proteus mirabilis, Staphylococcus agalactiae, or Staphylococcus maltophilia (see paragraph [0440]).
Regarding present claims 98 and 102, Gootenberg discloses detecting the nucleic acid from a parasite such as Giardia lamblia (see paragraph [0246]).
Regarding present claims 104 and 106, Gootenberg discloses detecting the nucleic acid from a protozoa such as Amoebozoa (see paragraphs [0396] and [0433]).
Present SEQ ID NO: 6 and SEQ ID NO: 4 in Gootenberg
Query Match 100.0%; Score 6717; Length 1281;
Best Local Similarity 100.0%;
Matches 1281; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MKKSIFDQFVNQYALSKTLRFELKPVGETGRMLEEAKVFAKDETIKKKYEATKPFFNKLH 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MKKSIFDQFVNQYALSKTLRFELKPVGETGRMLEEAKVFAKDETIKKKYEATKPFFNKLH 60
Qy 61 REFVEEALNEVELAGLPEYFEIFKYWKRYKKKFEKDLQKKEKELRKSVVGFFNAQAKEWA
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 REFVEEALNEVELAGLPEYFEIFKYWKRYKKKFEKDLQKKEKELRKSVVGFFNAQAKEWA 120
Qy 121 KKYETLGVKKKDVGLLFEENVFAILKERYGNEEGSQIVDESTGKDVSIFDSWKGFTGYFI
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 KKYETLGVKKKDVGLLFEENVFAILKERYGNEEGSQIVDESTGKDVSIFDSWKGFTGYFI 180
Qy 181 KFQETRKNFYKDDGTATALATRIIDQNLKRFCDNLLIFESIRDKIDFSEVEQTMGNSIDK
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 KFQETRKNFYKDDGTATALATRIIDQNLKRFCDNLLIFESIRDKIDFSEVEQTMGNSIDK 240
Qy 241 VFSVIFYSSCLLQEGIDFYNCVLGGETLPNGEKRQGINELINLYRQKTSEKVPFLKLLDK
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 VFSVIFYSSCLLQEGIDFYNCVLGGETLPNGEKRQGINELINLYRQKTSEKVPFLKLLDK 300
Qy 301 QILSEKEKFMDEIENDEALLDTLKIFRKSAEEKTTLLKNIFGDFVMNQGKYDLAQIYISR 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 QILSEKEKFMDEIENDEALLDTLKIFRKSAEEKTTLLKNIFGDFVMNQGKYDLAQIYISR 360
Qy 361 ESLNTISRKWTSETDIFEDSLYEVLKKSKIVSASVKKKDGGYAFPEFIALIYVKSALEQI
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 ESLNTISRKWTSETDIFEDSLYEVLKKSKIVSASVKKKDGGYAFPEFIALIYVKSALEQI 420
Qy 421 PTEKFWKERYYKNIGDVLNKGFLNGKEGVWLQFLLIFDFEFNSLFEREIIDENGDKKVAG
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 PTEKFWKERYYKNIGDVLNKGFLNGKEGVWLQFLLIFDFEFNSLFEREIIDENGDKKVAG 480
Qy 481 YNLFAKGFDDLLNNFKYDQKAKVVIKDFADEVLHIYQMGKYFAIEKKRSWLADYDIDSFY
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 YNLFAKGFDDLLNNFKYDQKAKVVIKDFADEVLHIYQMGKYFAIEKKRSWLADYDIDSFY 540
Qy 541 TDPEKGYLKFYENAYEEIIQVYNKLRNYLTKKPYSEDKWKLNFENPTLADGWDKNKEADN
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 TDPEKGYLKFYENAYEEIIQVYNKLRNYLTKKPYSEDKWKLNFENPTLADGWDKNKEADN 600
Qy 601 STVILKKDGRYYLGLMARGRNKLFDDRNLPKILEGVENGKYEKVVYKYFPDQAKMFPKVC
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 STVILKKDGRYYLGLMARGRNKLFDDRNLPKILEGVENGKYEKVVYKYFPDQAKMFPKVC 660
Qy 661 FSTKGLEFFQPSEEVITIYKNSEFKKGYTFNVRSMQRLIDFYKDCLVRYEGWQCYDFRNL
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 661 FSTKGLEFFQPSEEVITIYKNSEFKKGYTFNVRSMQRLIDFYKDCLVRYEGWQCYDFRNL 720
Qy 721 RKTEDYRKNIEEFFSDVAMDGYKISFQDVSESYIKEKNQNGDLYLFEIKNKDWNEGANGK
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 721 RKTEDYRKNIEEFFSDVAMDGYKISFQDVSESYIKEKNQNGDLYLFEIKNKDWNEGANGK 780
Qy 781 KNLHTIYFESLFSADNIAMNFPVKLNGQAEIFYRPRTEGLEKERIITKKGNVLEKGDKAF
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 781 KNLHTIYFESLFSADNIAMNFPVKLNGQAEIFYRPRTEGLEKERIITKKGNVLEKGDKAF 840
Qy 841 HKRRYTENKVFFHVPITLNRTKKNPFQFNAKINDFLAKNSDINVIGVDRGEKQLAYFSVI
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 841 HKRRYTENKVFFHVPITLNRTKKNPFQFNAKINDFLAKNSDINVIGVDRGEKQLAYFSVI 900
Qy 901 SQRGKILDRGSLNVINGVNYAEKLEEKARGREQARKDWQQIEGIKDLKKGYISQVVRKLA
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 901 SQRGKILDRGSLNVINGVNYAEKLEEKARGREQARKDWQQIEGIKDLKKGYISQVVRKLA 960
Qy 961 DLAIQYNAIIVFEDLNMRFKQIRGGIEKSVYQQLEKALIDKLTFLVEKEEKDVEKAGHLL
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 961 DLAIQYNAIIVFEDLNMRFKQIRGGIEKSVYQQLEKALIDKLTFLVEKEEKDVEKAGHLL 1020
Qy 1021 KAYQLAAPFETFQKMGKQTGIVFYTQAAYTSRIDPVTGWRPHLYLKYSSAEKAKADLLKF
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1021 KAYQLAAPFETFQKMGKQTGIVFYTQAAYTSRIDPVTGWRPHLYLKYSSAEKAKADLLKF 1080
Qy 1081 KKIKFVDGRFEFTYDIKSFREQKEHPKATVWTVCSCVERFRWNRYLNSNKGGYDHYSDVT
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1081 KKIKFVDGRFEFTYDIKSFREQKEHPKATVWTVCSCVERFRWNRYLNSNKGGYDHYSDVT 1140
Qy 1141 KFLVELFQEYGIDFERGDIVGQIEVLETKGNEKFFKNFVFFFNLICQIRNTNASELAKKD
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1141 KFLVELFQEYGIDFERGDIVGQIEVLETKGNEKFFKNFVFFFNLICQIRNTNASELAKKD 1200
Qy 1201 GKDDFILSPVEPFFDSRNSEKFGEDLPKNGDDNGAFNIARKGLVIMDKITKFADENGGCE
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1201 GKDDFILSPVEPFFDSRNSEKFGEDLPKNGDDNGAFNIARKGLVIMDKITKFADENGGCE 1260
Qy 1261 KMKWGDLYVSNVEWDNFVANK 1281
|||||||||||||||||||||
Db 1261 KMKWGDLYVSNVEWDNFVANK 1281
Claim Rejections - 35 USC § 103
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 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.
Claims 8 and 21 are rejected under 35 U.S.C. 103(a) as being unpatentable over Gootenberg et al. (US Patent Application Publication US 2023/0127948) as applied to claim 1 and further in view of Tsou et al., (Translational Oncology, 2019) and Doudna et al. (US Patent Application Publication US 2023/0357761).
Gootenberg et al. teach the claimed invention as discussed above. They do not teach FAM-Q reporter or the unspecific nucleases Csx1, Cap4, Can1, or NucC.
Tsou teaches methods of detecting viral nucleic acids comprising using CRISPR and Cas12 and using FAM-Q reporter (see page 1567 under Fluorescent Readout of CRISPR Cas12 activity using FAM- Quencher and Results).
It would have been prima facie obvious to employ the FAM-Q quencher of Tsou in the method of Gootenberg because Tsou teaches that FAM-Q quencher enables convenient detection of circulating nucleic acid targets in body fluids (see Abstract and Results).
Doudna teaches Can1 and NucC non-specific nucleases used in methods of detecting nucleic acids that employ CRISPR. Doudna teaches that Cas proteins Cas12 or Cas13 group, and type III accessory nucleases including Csm6, Csx1, Can1, NucC and any other proteins that contain a cA-binding “sensor” domain and an effector nuclease domain as well as homologues, orthologues, and/or functional fragments of any Type III accessory nuclease (see paragraph [0064]).
Doudna teaches (in paragraph [0088]) The Type III accessory Cas nucleases include but are not limited to Csm6, and Csx1, Can1, NucC and any other proteins or homologues, orthologues or functional fragments thereof that contain a CARF “sensor” domain and an effector nuclease domain activators disclosed herein include any molecule (e.g., RNA) which generates sustained activation (e.g., by limiting or preventing self-inactivating mechanisms such as degradation of the activator by the activated protein) of the Cas protein as a non-specific nuclease while maintaining the fast kinetics. The molecules (also referred to as “RNA activators” or “activation sequences” or “activators”) can be modified in any way to provide sustained, robust activation as compared to cyclic and/or linear oligoadenylates currently used. Once activated, the Cas protein cleaves RNA indiscriminately, similar to the collateral effect of Cas13 enzymes. Thus, in addition to detection effector modification of reporter constructs, the activated Type III enzyme can be used in conjunction with another CRISPR enzyme (e.g., Cas13, Cas12 or Cas14) for signal amplification. Thus, the activators can be used to increase sensitivity of the assay and decrease cost.
It would have been prima facie obvious to employ Doudna’s Csx1, Can1, NucC in the methods of Gootenberg because Doudna teaches that the Csx1, Can1, NucC activators can be used to increase sensitivity of the assay and decrease cost.
Thus, the present invention would have been prima facie obvious at the time the invention was made.
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 §§ 706.02(l)(1) - 706.02(l)(3) 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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1, 2, 7-9, 11, 19-21, 41, 77, 94-96, 98, 100, 102, and 104-109 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 2531, 33-39, and 71-75 of copending Application No. 17/607,970.
Present claims are drawn to a method for determining the presence of viral, SARS-CoV-2 and bacterial nucleic acids in a sample, the method comprising contacting the sample with a CRISPR/Cas complex comprising an effector nuclease and a guide RNA encoding a nucleic acid that hybridizes to a target nucleic acid, Cas12 nuclease, wherein the one or more nucleases is not the same as the effector nuclease, one or more oligonucleotides, and a fluorescence reporter, and measuring a fluorescence signal emitted from the fluorescence reporter, wherein a presence of the fluorescence signal indicates the presence of the target nucleic acid in the sample.
The claims of the copending application 17/607,970 are drawn to An engineered system comprising: a. a Cas12a.1 protein comprising an amino acid sequence of SEQ ID NO: 3, or at least 90% sequence identity thereto, a Cas12p protein comprising an amino acid sequence of SEQ ID NO: 4, or at least 90% sequence identity thereto, or a Cas12q protein comprising an amino acid sequence of SEQ ID NO: 5 or 222, or at least 90% sequence identity thereto, or a nucleic acid encoding the Cas12a_1, Cas12p, or Cas12q protein; and b. a Cas12a.1, Cas12p, or Casl12q gRNA, or a nucleic acid encoding a Cas 12a.1, Cas12p, or Cas12q gRNA, wherein the gRNA and the Cas12a.1, Cas12p, or Cas12q protein do not naturally occur together, wherein the gRNA is capable of hybridizing to a target sequence in a target DNA, and the gRNA is capable of forming a complex with the Cas12a.1, Cas12p, or Cas12q protein. The copending application 17/607,970 discloses a Cas12 sequence identical with present SEQ ID NO: 6 (see SEQ ID NO: 4).
Although the claims at issue are not identical, they are not patentably distinct from each other because the present claims and the claims of the copending application are drawn to similar methods of detecting nucleic acids in a sample comprising using the CRISPR/Cas12. The claims of the present application differ in that they recite the method step in a different order.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AGNIESZKA BOESEN whose telephone number is (571)272-8035. The examiner can normally be reached on 8:30 - 5:00 PM.
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, Thomas Visone can be reached on 571-270-0684. 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.
/AGNIESZKA BOESEN/Primary Examiner, Art Unit 1648