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 .
Claims 1-32 are currently pending and under examination.
Priority
Acknowledgment is made of applicant' s claim for foreign priority under 35 U.S.C. 119 (a)-(d). Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The Information Disclosure Statements filed April 29, 2022; April 29, 2022; and May 14, 2024 have been considered.
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.
Regarding claim 1, Carpenter teaches a method of obtaining an enriched population of a target polynucleotide (Abstract). Carpenter teaches purifying a population of mRNA molecules from a sample obtained from a subject (Page 9, [0068], Pages 9-10, [0071], Page 8, [0055], Page 17, [0180]-[0181] and Page 23, [0230]). Carpenter teaches preparing cDNA from the mRNA molecules of step (i) (Page 8, [0043] and [0055]). Carpenter teaches amplifying 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] 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 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).
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 purifying a population of mRNA molecules from a sample obtained from a subject (Page 9, [0068], Pages 9-10, [0071], Page 8, [0055], Page 17, [0180]-[0181] and Page 23, [0230]). Carpenter teaches preparing cDNA from the mRNA molecules of step (i) (Page 8, [0043] and [0055]). Carpenter teaches amplifying 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] 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).
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 20, 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 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.
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.
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, so it would be obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to perform a method of obtaining an enriched population of a target polynucleotide and perform a method of obtaining a pool of target-irrelevant synthetic single guide RNAs (sgRNAs) for a sgRNA-guided nucleic acid-binding Cas protein using those same steps.
Therefore, the claims are not deemed to be patentably distinct.
Conclusion
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/JESSICA D PARISI/Examiner, Art Unit 1684
/HEATHER CALAMITA/Supervisory Patent Examiner, Art Unit 1684