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 cancels claims 3 and 20. Claims 1-2, 4-19 and 21-32 are currently pending and under examination.
Any objection or rejection of record in the previous Office Action, which is not addressed in this action has been withdrawn in light of Applicant’s amendments and/or arguments. This action is Final.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 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 1-14 and 16-32 are rejected under 35 U.S.C. 102 (a)(1) and (a)(2) as being anticipated by Carpenter et al. (U.S. Patent Application Publication US 2018/0298421 A1, published October 18, 2018), cited on the IDS filed April 29, 2022. This rejection is maintained and modified as necessitated by amendments.
Regarding claim 1, Carpenter teaches a method of obtaining an enriched population of a target polynucleotide (Abstract). Carpenter teaches preparing cDNA from a population of mRNA molecules purified from a sample obtained from a subject (Page 9, [0068], Pages 9-10, [0071], Page 10, [0074], Page 8, [0055], Page 17, [0180]-[0181], Page 19, [0192], Page 23, [0230], Page 8, [0043], Page 27, [0252] and [0055]). Carpenter teaches amplifying with polymerase chain reaction (PCR) one or more target sequences from the cDNA obtained in step (ii) to obtain a pool of DNA molecules (Pages 1-2, [0010], Page 3, [0012], Page 5, [0043] and [0055], Page 11, [0106], Pages 18-19, [0187], Page 19, [0192] and Page 22, [0209]-[0210]). Carpenter teaches fragmenting the amplified DNA molecules to obtain fragments (Pages 1-2, [0010] and Pages 6-7, [0021]). Carpenter teaches connecting the fragments of step (iv) to a tag to yield a pool of tagged catcher oligonucleotides (Pages 1-2, [0010], Page 7, [0036] Page 11, [0106], Pages 15-16, [0163], Pages 18-19, [0187], Page 19, [0191]-[0192], Page 27, [0249] and Examples 3-6). Carpenter teaches hybridizing a pool of starting oligonucleotides and said tagged catcher oligonucleotide(s) (Pages 6-7, [0021], Page 11, [0106], Page 13, [0127], Pages 18-19, [0186]-[0187], Tables 1-2 and Examples 2-6 and 9). Carpenter teaches said starting oligonucleotides comprises a promoter segment, a random segment as potentially complementary sequence for the catcher oligonucleotide and a binding segment, which is complementary to at least a portion of a scaffold sequence for interaction with a single guide RNA(sgRNA)-guided nucleic acid-binding protein (Pages 1-2, [0010], Page 7, [0026], Page 10, [0074]-[0075], Page 11, [0099], Page 13, [0127] and [0135], Page 14, [0144], Tables 1-2 and Examples 1-3 and 9). Carpenter teaches removing complexes of starting oligonucleotides and tagged catcher oligonucleotides from said pool of starting oligonucleotides by binding said tag to a cognate interactor, thereby obtaining a reduced pool of starting oligonucleotides (Pages 1-2, [0010], Pages 6-7, [0021] Page 19, [0191]-[0192] and Example 9). Carpenter teaches preparing a pool of sgRNAs with said reduced pool of starting oligonucleotides obtained in step (Page 11, [0106], Pages 18-19, [0187] and Examples 3-6). Carpenter teaches cleaving a mixture of polynucleotides obtained from a test sample with an sgRNA-guided nucleic acid-binding protein using the pool of sgRNAs obtained in step (viii) to obtain a mixture of cut and uncut polynucleotides (Pages 4-5, [0015]-[0016], Page 7, [0024], Page 18, [0184]-[0185] and Page 19, [0191]-[0192]). Carpenter teaches size selecting one or more uncut target polynucleotides from said mixture of cut and uncut polynucleotides obtained in step (ix) (Pages 6-7, [0021], Page 7, [0024]-[0026], Pages 18-19, [0187] and Example 6). Carpenter teaches using these methods allows for the reduced cost of sequencing and improve data yield (Page 11, [0100] and [0108]).
Regarding claim 2, Carpenter teaches a method of obtaining a pool of personalized target- irrelevant synthetic single guide RNAs (sgRNAs) for a sgRNA-guided nucleic acid-binding protein comprising (Pages 1-2, [0010], Page 5, [0017], Page 7, [0028], Page 11, [0106], Pages 18-19, [0187], Page 16, [0168], Pages 16-17, [0174] and Examples 3-6 and 10). Carpenter teaches preparing cDNA from a population of mRNA molecules purified from a sample obtained from a subject (Pages 1-2, [0010], Page 3, [0012], Page 19, [0192], Page 9, [0068], Pages 9-10, [0071], Page 10, [0074], Page 8, [0055], Page 17, [0180]-[0181], Page 23, [0230], Page 8, [0043], Page 27, [0252] and [0055]). Carpenter teaches amplifying with polymerase chain reaction (PCR) one or more target sequences from the cDNA obtained in step (ii) to obtain a pool of DNA molecules (Pages 1-2, [0010], Page 3, [0012], Page 5, [0043] and [0055], Page 11, [0106], Pages 18-19, [0187], Page 19, [0192] and Page 22, [0209]-[0210]). Carpenter teaches fragmenting the amplified DNA molecules to obtain fragments (Pages 1-2, [0010] and Pages 6-7, [0021]). Carpenter teaches connecting the fragments of step (iv) to a tag to yield a pool of tagged catcher oligonucleotides (Pages 1-2, [0010], Page 7, [0036] Page 11, [0106], Pages 15-16, [0163], Pages 18-19, [0187], Page 19, [0191]-[0192], Page 27, [0249] and Examples 3-6). Carpenter teaches hybridizing a pool of starting oligonucleotides and said tagged catcher oligonucleotide(s) (Pages 6-7, [0021], Page 11, [0106], Page 13, [0127], Pages 18-19, [0186]-[0187], Tables 1-2 and Examples 2-6 and 9). Carpenter teaches said starting oligonucleotides comprises a promoter segment, a random segment as potentially complementary sequence for the catcher oligonucleotide and a binding segment, which is complementary to at least a portion of a scaffold sequence for interaction with a single guide RNA(sgRNA)-guided nucleic acid-binding protein (Pages 1-2, [0010], Page 7, [0026], Page 10, [0074]-[0075], Page 11, [0099], Page 13, [0127] and [0135], Page 14, [0144], Tables 1-2 and Examples 1-3 and 9). Carpenter teaches removing complexes of starting oligonucleotides and tagged catcher oligonucleotides from said pool of starting oligonucleotides by binding said tag to a cognate interactor, thereby obtaining a reduced pool of starting oligonucleotides (Pages 1-2, [0010], Pages 6-7, [0021] Page , [0191]-[0192] and Example 9). Carpenter teaches preparing a pool of sgRNAs with said reduced pool of starting oligonucleotides (Page 11, [0106], Pages 18-19, [0187] and Examples 3-6). Carpenter teaches using these methods allows for the reduced cost of sequencing and improve data yield (Page 11, [0100] and [0108]).
Regarding claim 3, Carpenter teaches said amplification (iii) is performed as polymerase chain reaction (PCR) (Pages 1-2, [0010], Page 3, [0012] and Page 19, [0192]).
Regarding claim 4, Carpenter teaches said tag is biotin and said cognate interactor is streptavidin (Page 19, [0191]-[0192] and Example 9).
Regarding claim 5, Carpenter teaches said step of connecting the fragments to a biotin tag comprises an end-tailing with activated biotin, a ligation reaction with biotin or a linkage to biotin via click chemistry (Page 19, [0191]-[0192], Example 9 and Fig. 10).
Regarding claim 6, Carpenter teaches the sgRNA-guided nucleic acid-binding protein is a DNA binding Cas protein (Pages 1-2, [0010]).
Regarding claim 7, Carpenter teaches the DNA binding Cas protein is a member of the family of Cas9 proteins (Pages 1-2, [0010]).
Regarding claim 8, Carpenter teaches said random segment comprises between about 10 to 30 random nucleotides (Tables 1 and 2)
Regarding claim 9, Carpenter teaches steps (vi) and (vii) are repeated 1, 2, 3, 4, 5 or more times (e.g., serially processed for host nucleic acids and then repeated for non-host nucleic acids and repeated by hybridizing to different targets Page 5, [0017], Page 7, [0022] and Page 11, [0106]).
Regarding claim 10, Carpenter teaches said one or more target polynucleotides or target sequences comprise a gene or panel of genes (Page 22, [0214] and Page 29, [0270]).
Regarding claim 11, Carpenter teaches a step of sequencing said size selected uncut target polynucleotide(s) (Pages 6-7, [0021], Page 7, [0024]-[0026], Pages 18-19, [0187] and Example 6).
Regarding claim 12, Carpenter teaches a kit comprising a pool of sgRNAs obtainable by the method of any one of claim 2 and an sgRNA-guided nucleic acid-binding protein (see Claim 2 above and Page 6, [0020])
Regarding claim 13, Carpenter teaches a method for removing target-irrelevant polynucleotides from a mixture of polynucleotides in a Cas9-based endonuclease assay, the method comprising using the pool of sgRNAs obtained by the method of claim 2 (see Claim 2 above, Page , [0197] and Example 8) .
Regarding claim 14, Carpenter teaches a method of monitoring a disease state performing the method of any one of claim 1 in a predefined interval of time (see Claim 1 above and Examples 4 and 5).
Regarding claim 16, Carpenter teaches fragmenting the amplified DNA molecules produces fragments of a size 20 to 30 bp (Page 12, [0117] and Page 20, [0197]).
Regarding claim 17, Carpenter teaches the cognate interactor is located on a bead or a surface (Page 19, [0191]-[0192] and Example 9).
Regarding claim 18, Carpenter teaches the DNA binding Cas protein is a Cas9 protein or a derivative thereof (Pages 1-2, [0010]).
Regarding claim 19, Carpenter teaches a random segment comprises 20 random nucleotides (Tables 1 and 2).
Regarding claim 21, Carpenter teaches said tag is biotin and said cognate interactor is streptavidin (Page 19, [0191]-[0192] and Example 9).
Regarding claim 22, Carpenter teaches said step of connecting the fragments to a biotin tag comprises an end-tailing with activated biotin, a ligation reaction with biotin or a linkage to biotin via click chemistry (Page 19, [0191]-[0192], Example 9 and Fig. 10).
Regarding claim 23, Carpenter teaches the sgRNA-guided nucleic acid-binding protein is a DNA binding Cas protein (Pages 1-2, [0010]).
Regarding claim 24, Carpenter teaches the DNA binding Cas protein is a member of the family of Cas9 proteins (Pages 1-2, [0010]).
Regarding claim 25, Carpenter teaches the DNA binding Cas protein is a Cas9 protein or a derivative thereof (Pages 1-2, [0010]).
Regarding claim 26, Carpenter teaches said random segment comprises between about 10 to 30 random nucleotides (Tables 1 and 2).
Regarding claim 27, Carpenter teaches said random segment comprises 20 random nucleotides (Tables 1 and 2).
Regarding claim 28, Carpenter teaches steps (vi) and (vii) are repeated 1, 2, 3, 4, 5 or more times (e.g., serially processed for host nucleic acids and then repeated for non-host nucleic acids and repeated by hybridizing to different targets Page 5, [0017], Page 7, [0022] and Page 11, [0106]).
Regarding claim 29, Carpenter teaches said one or more target polynucleotides or target sequences comprise a gene or panel of genes (Page 22, [0214] and Page 29, [0270]).
Regarding claim 30, Carpenter teaches fragmenting the amplified DNA molecules produces fragments of a size 20 to 30 bp (Page 12, [0117] and Page 20, [0197]).
Regarding claim 31, Carpenter teaches the cognate interactor is located on a bead or a surface (Page 19, [0191]-[0192] and Example 9).
Regarding claim 32, Carpenter teaches the sgRNA-guided nucleic acid-binding protein is a Cas9 protein or derivative thereof (Pages 1-2, [0010] and Pages 5-6, [0019]-[0020]).
Carpenter teaches each and every limitation of claims 1-14 and 16-32, therefore Carpenter anticipates claims 1-14 and 16-32.
Claim 15 is rejected under 35 U.S.C 103 as being unpatentable over Carpenter et al. (U.S. Patent Application Publication US 2018/0298421 A1, published October 18, 2018), cited on the IDS filed April 29, 2022, as applied to claims 1-14 and 16-32 above, in view of DeRisi et al. (U.S. Patent Application Publication US 2018/0051320 A1, published February 22, 2018), cited on the IDS filed April 29, 2022. This rejection is maintained and modified as necessitated by amendments.
Regarding claim 15, Carpenter teaches monitoring a disease as discussed above. Carpenter teaches target sequence for depletion are followed by a PAM sequence (Pages 1-2, [0010]).
Carpenter does not explicitly teach or suggest said disease is cancer.
DeRisi teaches depletion of sequences, pooling and sequencing using CRISPR/CAS9 sgRNA complexes (Page 1, [0006], Page 7, [0064], Page 11, [0089] and [0096], Page 14, [0116] and Fig. 1). DeRisi teaches cleaving target sequences and amplifying non cleaved targets (Page 1, [0007]). DeRisi teaches using the disclosed methods to monitor cancer (Page 8, [0075], Page 9, [0084], Page 13, [0111]-[0112] and Page 15, [0125]). DeRisi teaches the DASH (Depletion of Abundant Sequences by Hybridization) method can be adapted to target any sequence containing a PAM site as well as may be adapted for any sample type (Page 15, [0123] and Page 1, [0006]). DeRisi teaches the DASH method improves on the input requirements, performance, programmability, increasing sequencing yield and cost (Page 14, [0119] and Page 1, [0006]).
As a common field of endeavor, both Carpenter and DeRisi teach methods for depletion of sequences, pooling and sequencing using CRISPR/CAS9 sgRNA complexes.
It would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to modify the teachings of Carpenter with the teachings of DeRisi using the DASH method to monitor specifically cancer. Using the DASH method allows for improved input requirements, performance, programmability, increasing sequencing yield and reducing cost as taught by DeRisi (Page 14, [0119] and Page 1, [0006]). Additionally the methods of DeRisi are well suited for the methods of Carpenter and would have reasonable expectations of success without unexpected results because DeRisi teaches the DASH (Depletion of Abundant Sequences by Hybridization) method can be adapted to target any sequence containing a PAM site as well as may be adapted for any sample type (Page 15, [0123] and Page 1, [0006]).
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-2, 4, 6-12 and 16-32 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 4-9, 11-12, 16-19, 21-26 and 28-32 of U.S. Patent No. 11,572,554 in view of Carpenter et al. (U.S. Patent Application Publication US 2018/0298421 A1, published October 18, 2018), cited on the IDS filed April 29, 2022. This is a new rejection as necessitated by amendments.
Although the claims at issue are not perfectly identical, they are not patentably distinct from each other because the preambles are mostly identical, as well as it also appears that a majority of the steps of the claims are also identical.
The instant claims are drawn to a method of obtaining an enriched population of a target polynucleotide as well as a method of obtaining a pool of target irrelevant synthetic sgRNAs for a sgRNA-guided nucleic acid-binding protein comprising preparing cDNA from a population of mRNA molecules purified from a sample obtained from a subject the mRNA amplifying with polymerase chain reaction (PCR) one or more target sequences from the cDNA to obtain a pool of tagged catcher oligonucleotides hybridized to starter oligonucleotides, comprising a promoter segment, a random segment, and a binding segment, wherein the binding segment is complementary to at least a portion of a scaffold oligonucleotide for interaction with a single guide RNAs (sgRNA) nucleic acid-binding protein and removing complexes of starting oligonucleotides and tagged catcher oligonucleotides from said pool of starting oligonucleotides by binding said tag to a cognate interactor, thereby obtaining a reduced pool of starting oligonucleotides and preparing a pool of sgRNAs with said reduced pool of starting oligonucleotides as well as cleaving a mixture of polynucleotides obtained from a test sample with an sgRNA-guided nucleic acid-binding protein using the pool of sgRNAs to obtain a mixture of cut and uncut polynucleotides and size selecting one or more uncut target polynucleotides from said mixture of cut and uncut polynucleotides.
U.S. Patent 11,572,544 claims are drawn to a method of obtaining an enriched population of a target polynucleotide as well as a method of obtaining a pool of target irrelevant synthetic sgRNAs for a sgRNA-guided nucleic acid-binding protein comprising a obtain a pool of tagged catcher oligonucleotides hybridized to starter oligonucleotides, comprising a promoter segment, a random segment, and a binding segment, wherein the binding segment is complementary to at least a portion of a scaffold oligonucleotide for interaction with a single guide RNAs (sgRNA) nucleic acid-binding protein and removing complexes of starting oligonucleotides and tagged catcher oligonucleotides from said pool of starting oligonucleotides by binding said tag to a cognate interactor, thereby obtaining a reduced pool of starting oligonucleotides and preparing a pool of sgRNAs with said reduced pool of starting oligonucleotides as well as cleaving a mixture of polynucleotides obtained from a test sample with an sgRNA-guided nucleic acid-binding protein using the pool of sgRNAs to obtain a mixture of cut and uncut polynucleotides and size selecting one or more uncut target polynucleotides from said mixture of cut and uncut polynucleotides (Claims 1, 2 and 10).
U.S. Patent 11,572,544 fails to claim preparing cDNA from a population of mRNA molecules purified from a sample obtained from a subject the mRNA amplifying with polymerase chain reaction (PCR) one or more target sequences from the cDNA.
However, Carpenter discloses a method of obtaining an enriched population of a target polynucleotide as well as a method of obtaining a pool of personalized target- irrelevant synthetic single guide RNAs (sgRNAs) for a sgRNA-guided nucleic acid-binding protein comprising (Abstract, Pages 1-2, [0010], Page 5, [0017], Page 7, [0028], Page 11, [0106], Pages 18-19, [0187], Page 16, [0168], Pages 16-17, [0174] and Examples 3-6 and 10). Carpenter discloses preparing cDNA from a population of mRNA molecules purified from a sample obtained from a subject (Page 9, [0068], Pages 9-10, [0071], Page 10, [0074], Page 8, [0055], Page 17, [0180]-[0181], Page 19, [0192], Page 23, [0230], Page 8, [0043], Page 27, [0252] and [0055]). Carpenter discloses amplifying with polymerase chain reaction (PCR) one or more target sequences from the cDNA obtained in step (ii) to obtain a pool of DNA molecules (Pages 1-2, [0010], Page 3, [0012], Page 5, [0043] and [0055], Page 11, [0106], Pages 18-19, [0187], Page 19, [0192] and Page 22, [0209]-[0210]). Carpenter discloses fragmenting the amplified DNA molecules to obtain fragments (Pages 1-2, [0010] and Pages 6-7, [0021]). Carpenter discloses connecting the fragments of step (iv) to a tag to yield a pool of tagged catcher oligonucleotides (Pages 1-2, [0010], Page 7, [0036] Page 11, [0106], Pages 15-16, [0163], Pages 18-19, [0187], Page 19, [0191]-[0192], Page 27, [0249] and Examples 3-6). Carpenter discloses hybridizing a pool of starting oligonucleotides and said tagged catcher oligonucleotide(s) (Pages 6-7, [0021], Page 11, [0106], Page 13, [0127], Pages 18-19, [0186]-[0187], Tables 1-2 and Examples 2-6 and 9). Carpenter discloses said starting oligonucleotides comprises a promoter segment, a random segment as potentially complementary sequence for the catcher oligonucleotide and a binding segment, which is complementary to at least a portion of a scaffold sequence for interaction with a single guide RNA(sgRNA)-guided nucleic acid-binding protein (Pages 1-2, [0010], Page 7, [0026], Page 10, [0074]-[0075], Page 11, [0099], Page 13, [0127] and [0135], Page 14, [0144], Tables 1-2 and Examples 1-3 and 9). Carpenter discloses removing complexes of starting oligonucleotides and tagged catcher oligonucleotides from said pool of starting oligonucleotides by binding said tag to a cognate interactor, thereby obtaining a reduced pool of starting oligonucleotides (Pages 1-2, [0010], Pages 6-7, [0021] Page 19, [0191]-[0192] and Example 9). Carpenter discloses preparing a pool of sgRNAs with said reduced pool of starting oligonucleotides obtained in step (Page 11, [0106], Pages 18-19, [0187] and Examples 3-6). Carpenter discloses cleaving a mixture of polynucleotides obtained from a test sample with an sgRNA-guided nucleic acid-binding protein using the pool of sgRNAs obtained in step (viii) to obtain a mixture of cut and uncut polynucleotides (Pages 4-5, [0015]-[0016], Page 7, [0024], Page 18, [0184]-[0185] and Page 19, [0191]-[0192]). Carpenter discloses size selecting one or more uncut target polynucleotides from said mixture of cut and uncut polynucleotides obtained in step (ix) (Pages 6-7, [0021], Page 7, [0024]-[0026], Pages 18-19, [0187] and Example 6).
It would be obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have combined the use of Carpenter’s cDNA from a population of mRNA and amplifying a target sequence from the cDNA in a method of obtaining an enriched population of a target polynucleotide and/or perform a method of obtaining a pool of target-irrelevant synthetic single guide RNAs (sgRNAs) for a sgRNA-guided nucleic acid-binding Cas protein, as claimed by the instant application and U.S. Patent 11,572,544 to allow for the reduced cost of sequencing and improve data yield as demonstrated by Carpenter (Page 11, [0100] and [0108]).
Response to Arguments
Applicant’s arguments and amendments filed May 22, 2026, with respect to the double patenting rejection have been fully considered and are deemed to be persuasive. Therefore this rejection has been withdrawn.
However, upon further consideration a new double patenting rejection is made as set forth above in view of Applicant’s amendments.
Applicant’s arguments and amendments filed May 22, 2026, with respect to the rejections under 35 U.S.C. § 102 and 103 have been fully considered, but they are not persuasive. Therefore these rejections are maintained as set forth above and discussed below.
Applicant asserts “Applicant's methods utilize a subject's mRNA to generate cDNA, from which a pool of catcher oligonucleotides is obtained. It is these catcher oligonucleotides that are then tagged and used to generate a pool of sgRNA. Put simply, Applicant's method relies on catcher oligonucleotides to generate a pool of sgRNAs”. As discussed above, Carpenter discloses using a subjects mRNA to generate cDNA in Page 8, [0055], Page 10, [0074] and most specifically Page 27, [0252], “A human blood sample carrying a known pathogen (e.g., Ebola) or an unknown pathogen is obtained and RNA is extracted (e.g., using a PAXgene Blood RNA extraction kit, Qiagen) and converted into a sequencing library using standard methods (e.g., using a KAPA RNA-seq library preparation kit). After cDNA creation and adapter ligation, the library is then mixed with Cas9 and a guide RNA pool”. Additionally, It is not proper to import claim limitations from the specification or outside knowledge into the claims. “Though understanding the claim language may be aided by explanations contained in the written description, it is important not to import into a claim limitations that are not part of the claim. For example, a particular embodiment appearing in the written description may not be read into a claim when the language is broader than the embodiment.” Superguide Corp. v. Direc TV Enterprises, Inc., 358 F.3d 870, 875, 69 USPQ2d 1865, 1868 (Fed. Cir. 2004). Independent claims 1 and 2 currently state in newly labeled step vii) “preparing a pool of sgRNA with said reduced pool of starting oligonucleotides obtained in step (vi)”, which is broadly interpreted as combining a pool of sgRNA’s with the reduced pool of starting oligonucleotides, the independent claims do not disclose the limitation that the catcher oligos prepare or generate the sgRNA or describe how the sgRNAs are to be prepared with the catcher oligos.
Applicant asserts “Carpenter does not disclose tagged catcher oligonucleotides nor obtaining a pool of tagged catcher oligonucleotides as recited by the solicited claims”.
As discloses by the instant specification in Page 19, Last Paragraph “The term "tag" as used herein relates to a molecule which is capable of binding to a cognate interactor and thereby be pulled out of a liquid solution or mixture of molecules. Examples of suitable tags and interactors are a biotin tag, e.g. DNA fragments obtained with steps described above, yielding "catcher oligonucleotides" and a streptavidin interactor”, describing a catcher oligo being a biotin tagged oligonucleotide that interacts with streptavidin. As discussed above, Carpenter discloses “DNA comprises a biotin label … binding to streptavidin beads” at page 92, [0191] and “a DNA mixture ([pooling]) (containing >95% unwanted human DNA, and <5% other DNA of interest) is fragmented, end-repaired and ligated to adapters following regular protocols, then amplified by PCR using primers of Biotin-P5 … this ensures that the entire sequencing library posses a 5’Biotin label” at Page 19, [0192], as well as in example 9, “DNA comprises a biotin label is purified by binding to streptavidin beads”. As discussed above Carpenter further discloses, the “guide RNAs are chosen to cleave multiple times in a pool of fragmented DNA” in example 6, “After cDNA creating and adapter ligation, the library is mixed with Cas9 and a guide RNA pool” in examples 4-5, and, “partitioning the mixture [(pooling)] into a first portion that includes the complementary target specific nucleic sequence present in the mixture that include a guide RNA/Cas9 complex and a second portion that includes fragmented extracted nucleic acid sequences that are not bound by a guide RNA/Cas9 complex, wherein the partitioning is performed using the affinity tag [(i.e., biotin)]” at Page 6, [0021], as well as “The compositions and methods of the invention can be utilized to serially process the nucleic acids in the sample… to arrive at a remaining pool of nucleic acids” at Page 11, [0106]. Therefore Carpenter does in indeed disclose tagged catcher oligonucleotides nor obtaining a pool of tagged catcher oligonucleotides.
Applicant asserts that “DeRisi was cited for its purported disclosure of using a method with the steps of depletion of sequences, pooling and sequencing using CRISPR/CAS9 sgRNA complexes to monitor cancer. (Office Action, at page 9). However, this disclosure in DeRisi does not cure Carpenter’s deficiencies with respect to claim 1”.
As discussed above, Carpenter does in fact disclose tagged catcher oligonucleotides nor obtaining a pool of tagged catcher oligonucleotides and the rejection is maintained and modified as set forth above.
Therefore, for all these reasons, and those listed above, Carpenter, as well as Carpenter in view DeRisi are deemed to render the instant invention anticipated/obvious.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
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/JESSICA D PARISI/ Examiner, Art Unit 1684
/HEATHER CALAMITA/ Supervisory Patent Examiner, Art Unit 1684
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