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 .
Status of the Applications, Amendments and/or Claims
This action is written in response to applicant's correspondence(s) submitted on 03/24/2025. In the paper of 03/24/2025, Applicant amended claims 1, 7, 10, 12-13, 15 and 18 and 24 and newly canceled claims 5-6. Accordingly, claims 1, 7-10, 12-24 are pending and under review. Claims 2-6, 11 and 25-80 are canceled.
Response to Arguments
Moot and/or Withdrawn Objection(s) and/or Rejection(s)
The objection to the specification for containing embedded hyperlink and/or other form of browser-executable code on page 55, para [202] is withdrawn based on the specification amendments submitted on 03/24/2025.
The rejection of claim 10 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite is withdrawn based on claim amendments.
The rejections of claims 5-6 under 35 U.S.C. 102(a)(1) as being anticipated by Kawano et al. (2010, Biotechniques 49(4):751-755) as evidenced by Warshawsky et al. (2011, Journal of clinical pathology, 64(10), pp.905-910) are moot based on cancellation of these claims.
The rejections of claims 5-6 under 35 U.S.C. 102(a)(1) as being anticipated by Warshawsky et al. (2011, Journal of clinical pathology, 64(10), pp.905-910) are moot based on cancellation of these claims.
The rejection of claims 1, 5-9,10, 12 and 20-24 under 35 U.S.C. 102(a)(1) as being anticipated by Warshawsky et al. (2011, Journal of clinical pathology, 64(10), pp.905-910) is withdrawn based on claimed amendments, particularly recitation of the limitation “terminal adaptor sequence”.
Concerning the instant “terminal adaptor sequence”, on page 2, para [07] of the specification, the disclosure states “The terminal adaptor sequences provide a universal site for primer hybridization so that clonal expansion of the desired DNA targets can be achieved and introduced into the automated sequencing processes used in NGS applications”. No additional structure or definition are provided.
Warshawsky et al. (2011) teach LNA capture probes but these probes do not provide a universal site for primer hybridization so that clonal expansion of the desired DNA targets can be achieved and introduced into the automated sequencing processes used in NGS applications.
The rejections of claims 5-6 on the ground of nonstatutory double patenting as being unpatentable over claims 1-2 of U.S. Patent No. 11,566,283 are moot based on cancellation of these claims.
The rejections of claims 5-6 on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 of U.S. Patent No. 10,266,889 are moot based on cancellation of these claims.
Maintained Rejection(s)
The rejection of claims 1, 7-10, 12-20 and 23 under 35 U.S.C. 102(a)(1) as being anticipated by Kawano et al. (2010, Biotechniques 49(4):751-755) as evidenced by Warshawsky et al. (2011, Journal of clinical pathology, 64(10), pp.905-910) is maintained with slight amendments necessitated by claim amendments.
The rejection of claims 21-22 and 24 under 35 U.S.C. 103 as being unpatentable over Kawano et al. (2010, Biotechniques 49(4):751-755) in view of Warshawsky et al. (2011, Journal of clinical pathology, 64(10), pp.905-910) and Behlke et al (US 2011/0117559) is maintained with slight amendments necessitated by claim amendments.
The rejection of claims 1, 7-10, 12-24 on the ground of nonstatutory double patenting as being unpatentable over claims 1-2 of U.S. Patent No. 11,566,283 is maintained with slight amendments necessitated by claim amendments.
The rejection of claims 1, 7-10, 12-24 on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 of U.S. Patent No. 10,266,889 is maintained with slight amendments necessitated by claim amendments.
Argument(s)
Applicant's remarks filed 03/24/2025 have been fully considered but they are not persuasive as follows.
Applicant presents no arguments or a rationale for traversing the rejection under 35 U.S.C. 102(a)(1) citing Kawano et al. (2010, Biotechniques 49(4):751-755) as evidenced by Warshawsky et al. (2011, Journal of clinical pathology, 64(10), pp.905-910).
Applicant presents no arguments or a rationale for why the rejection under 35 U.S.C. 102(a)(1) as being anticipated by Warshawsky et al. (2011, Journal of clinical pathology, 64(10), pp.905-910) are obviated by claim amendments, and presents no arguments or a rationale for why the claim rejections on the ground of nonstatutory double patenting as being unpatentable over claims of U.S. Patent No. 10,266,889 and/or the claims of U.S. Patent No. 11,566,283 should be withdrawn.
Claim Interpretation
Prior to analysis of the art, the claims must be construed. As noted in MPEP 2111, citing Phillips v. AWH Corp., 415 F.3d l303, 75 USPQ2d l321 (Fed. Cir. 2005), "During patent examination, the pending claims must be 'given their broadest reasonable interpretation consistent with the specification.' ".
Claim 1 recites the limitation, “an oligonucleotide having at least one Tm-enhancing group selected from the group consisting of a locked nucleic acid group, a bicyclic nucleic acid group, a C5-modified pyrimidine, a peptide nucleic acid group and combinations thereof,
wherein the oligonucleotide is configured to hybridize to a terminal adaptor sequence of a desired template nucleic acid from at least one member selected from a population of templates; and
wherein oligonucleotide is complementary to the terminal adaptor sequence of the desired template nucleic acid, wherein the oligonucleotide comprises at least one member selected from a blocker or a bait”.
Claim 1 as a whole is construed as claiming:
an oligonucleotide having at least one Tm-enhancing group selected from the group consisting a locked nucleic acid group, a bicyclic nucleic acid group, a C5-modified pyrimidine, a peptide nucleic acid group and combinations thereof, wherein the oligonucleotide has a complement sequence to an terminal adaptor sequence of a desired template in a population of templates and is configured to hybridize to the terminal adaptor sequence.
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.
Claims 1, 7-10, 12-20 and 23 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kawano et al. (2010, Biotechniques 49(4):751-755: previously cited) as evidenced by Warshawsky et al. (2011, Journal of clinical pathology, 64(10), pp.905-910: previously cited).
Kawano et al. (2010): claims 1,7-9, 17-19
Regarding claim 1 and 12-16, Kawano et al. teach the instant oligonucleotide which is a locked nucleic acid oligonucleotide (22 nucleotides in length) called “dimer eliminator-22”,
(5′-TACGAGATTTNNGATCGTCGGA-3′) (LNA nucleotides are underlined and also shown in italics, while NN shows random DNA) (see also in Fig. 1B, further reproduced below from pg 753, Fig. 1B).
Fig. 1B (from pg 753 of Kawano et al., 2010)
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The LNA “dimer-eliminator” oligonucleotide has at least one locked nucleotide (LNA) and is configured to be a complement sequence of an adapter-dimer ligation product and capable of partial hybridization to a terminal adapter sequence of a desired template of a population of templates.
Regarding claims 1 and 12, as shown in Fig. 1B as reproduced above, the LNA “dimer-eliminator” oligonucleotide of Kawano et al. is a blocker oligonucleotide, preventing the binding and extension of a RT primer to an adapter-dimer ligation product.
The LNA “dimer-eliminator” oligonucleotide of Kawano et al. provides a significant improvement to methods for construction of small RNA libraries for high through put sequencing as it reduces generation of libraries of adaptor-dimers that are devoid of inserts thereby meeting the limitation of claims 17-19 (see pg 751, abstract and pg 751, all text of the right col).
Regarding claims 1 and 7-10, the LNA “dimer eliminator-22” oligonucleotide of Kawano et al. meets the instant limitation of claim 1 as it is a “bait”/capture oligonucleotide for “adapter dimers” and is an oligonucleotide that comprises a plurality of locked nucleic acid group(s) i.e. the instant Tm-enhancing group(s).
Regarding claim 10, the locked nucleotides of the LNA “dimer eliminator-22” oligonucleotide of Kawano et al. provide a rise in the melting temperature of that oligonucleotide from about 1.4 ⁰C to about 25 ⁰C relative to an oligonucleotide having the same nucleotide sequence but no locked nucleotide(s) as Warshawsky et al. teach LNA is a nucleic acid analogue that contains a 2′-O,4′-C-methylene bridge in the ribose moiety and that where LNA bases are incorporated into any DNA oligonucleotide, each LNA base increases by 3-8°C the thermal stability with complementary DNA (Warshawsky et al., pg 1, 1st para of left col., below Conclusions).
Regarding claims 12-16, Kawano et al. teach a blocker-barcode domain comprising “about” 5 nucleotides arranged substantially contiguously i.e. the nucleotide sequence (5’-AGNNTTTA’-3).
Regarding claims 20 and 23, Kawano et al. teach a 3’ terminal modification (i.e. various LNAs/ locked nucleotides at 3’ terminus of the dimer-eliminator 22). Kawano et al. do not teach polymerase directed synthesis from the LNA “dimer eliminator-22” oligonucleotide of Kawano et al.
Accordingly, the instant claims 1, 7-10, 12-20 and 23 are anticipated by Kawano et al. (2010).
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 21-22 and 24 are rejected under 35 U.S.C. 103 as being unpatentable over Kawano et al. (2010, Biotechniques 49(4):751-755: previously cited) in view of Warshawsky et al. (2011, Journal of clinical pathology, 64(10), pp.905-910: previously cited) and Behlke et al (US 2011/0117559: previously cited).
The teachings of Kawano et al. as it relates to claims 1 and 16 are provided above.
Kawano et al. (2010, Biotechniques): claims 21-22 and 24
Regarding claims 21-22 and 24, Kawano et al. do NOT teach a locked nucleic acid oligonucleotide having a 3’ terminal modification selected from 3'-deoxynucleotide, 2',3'-dideoxynucleotide or a 3'-spacer C3 group), wherein the 3’ terminal modification prevents polymerase directed synthesis.
Regarding claims 21-22 and 24, Behlke et al. teach an oligonucleotide having a 3’ terminal modification that is a blocking moiety for preventing polymerase directed synthesis from the oligonucleotide (e.g. the terminal modification being 3’-deoxynucleotide, 2’,3’-dideoxynucleotide or a 3’-spacer C3 group: see SEQ ID NOS: 1 and 3, wherein SEQ ID NO: 1 of Behlke consists GGCTGGAGTGTAGCAGCAcGxxA, where x =C3 spacer and RNA base is lowercase; SEQ ID NO: 3 of Behlke consists ATTACGGGATACGGTGGATCGcCxxT, where x =C3 spacer and RNA base is lowercase).
Behlke disclosed (paragraph [0092]): "Alternatively abasic residues such as a C3 spacer may be incorporated in these locations to block primer extension."
Alternatively, Warshawsky et al. taught it already a matter of routine practice in the art to incorporate a 3’ C3 spacer as a 3’ terminal modification into LNA containing oligonucleotide useful for target sequence capture (see pg 2, left col., section entitled “NPM1 mutation detection” wherein Warshawsky et al. discloses a NPM1 LNA bait/capture oligonucleotide 5’- A*A*+G+ATCT+CT+G+GCA+GT+GG/3SpC3/–3′; where *, + and /3spC3/ refer to phosphorothioate, LNA and C3 spacer).
It would have been prima facie obvious to one of ordinary skill in the art to use a C3 spacer as a blocking group in the oligonucleotide suggested by the combined teachings of Warshawsky et al., since this was a known structure used to prevent primer extension, and thus represents nothing more than selecting an art recognized material for its intended purpose; see MPEP 2144.07.
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, 7-10, 12-24 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2 of U.S. Patent No. 11,566,283.
The instant claims are directed to oligonucleotide(s) comprising at least one Tm- enhancing group, wherein the at least one Tm-enhancing group is at least one member selected from the group consisting of a locked nucleic acid group, a bicyclic nucleic acid group, a C5-modified pyrimidine, a peptide nucleic acid group and combinations thereof, wherein oligonucleotide is complementary to a terminal adaptor sequence of a desired template within a population of templates.
while
claims 1-2 of U.S. Patent No. 11,566,283 are directed respectively to oligonucleotide(s) for use in a hybrid capture method of a desired template nucleic acid having a terminal adaptor sequence, wherein the oligonucleotide is selected from the group consisting of SEQ ID NOS: 10-16; and to
oligonucleotide(s) for use in a hybrid capture method of a desired template nucleic acid having a terminal adaptor sequence, wherein the oligonucleotide is selected from
(i) the group consisting of SEQ ID NOS: 2, 3, 4, 5, 6, 7 and 8;
(ii) the group consisting of SEQ ID NOS: 10, 11, 12, 13, 14, 15 and 16;
(iii) the group consisting of SEQ ID NOS: 18 and 19;
(iv) the group consisting of SEQ ID NOS: 21 and 22;
(v) the group consisting of SEQ ID NOS: 24 and 25;
(vi) the group consisting of SEQ ID NOS: 27 and 28;
(vii) SEQ ID NO: 30;
(viii) SEQ ID NO: 32,
(ix) SEQ ID NO: 34; and
(x) SEQ ID NO: 36, or a combination thereof.
Although the claims at issue are not identical, they are not patentably distinct from each other because the oligonucleotides of U.S. Patent No. 11,566,283 are oligonucleotides comprising at least one Tm enhancing group which anticipate the oligonucleotides of claims 1, 7-10, 12-24 of the instant application.
Claims 1, 7-10, 12-24 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 of U.S. Patent No. 10,266,889.
The instant claims are directed to oligonucleotide(s) comprising at least one Tm- enhancing group, wherein the at least one Tm-enhancing group is at least one member selected from the group consisting of a locked nucleic acid group, a bicyclic nucleic acid group, a C5-modified pyrimidine, a peptide nucleic acid group and combinations thereof, wherein oligonucleotide is complementary to a terminal adaptor sequence of a desired template in a population of templates.
while
claims 1-3 of U.S. Patent No. 10,266,889 are directed respectively to kit(s) comprising blocker oligonucleotide(s) for sequencing, the oligonucleotide(s) having a terminal adaptor sequence, wherein the oligonucleotide, wherein the oligonucleotide is selected from
(i) the group consisting of SEQ ID NOS: 2, 3, 4, 5, 6, 7 and 8;
(ii) the group consisting of SEQ ID NOS: 10, 11, 12, 13, 14, 15 and 16;
(iii) the group consisting of SEQ ID NOS: 18 and 19;
(iv) the group consisting of SEQ ID NOS: 21 and 22;
(v) the group consisting of SEQ ID NOS: 24 and 25;
(vi) the group consisting of SEQ ID NOS: 27 and 28;
(vii) SEQ ID NO: 30;
(viii) SEQ ID NO: 32,
(ix) SEQ ID NO: 34; and
(x) SEQ ID NO: 36, or a combination thereof.
Although the claims at issue are not identical, they are not patentably distinct from each other because the oligonucleotides of U.S. Patent No. 10,266,889 are oligonucleotides comprising at least one Tm enhancing group which anticipate the oligonucleotides of claims 1, 7-10, 12-24 of the instant application.
Conclusion
No claims are currently allowed.
THIS ACTION IS MADE FINAL. 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.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to OLAYINKA A OYEYEMI whose telephone number is (571)270-5956. The examiner can normally be reached Monday -Thursday: 9:00 am - 5:00 pm, EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, GARY Benzion can be reached on 571-272-0782. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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OLAYINKA A. OYEYEMI
Examiner
Art Unit 1681
/OLAYINKA A OYEYEMI/Examiner, Art Unit 1681
/GARY BENZION/Supervisory Patent Examiner, Art Unit 1681
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