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 .
Claim Status
Claims 1, 11, 13, and 14 are examined herein.
Claims 2-6, and 12 are withdrawn (see restriction/election below), and claims 7-10 are cancelled.
Information Disclosure Statement
All references from IDS(s) received 9/28/2023 have been considered unless marked with a strikethrough/cross out.
Election/Restrictions
Applicant’s election of Group I without traverse in the reply filed on 11/18/2025 is acknowledged. Applicant election of a single modified oligonucleotide with the chemical structure of the attached "detectable label" moiety. Further, applicant elects the chemical structure shown in claim 13. The elected specie reads on claims 1, 11, and 13. Claims 2-6 are withdrawn as not reading on the elected specie.
If the elected specie is not identified in the art, then Examiner will expand his search pursuant to MPEP 803.
The elected specie was identified in the art, and anticipatory art was found of the claims in the form of a nonstatutory double patenting rejection (see 103 rejection, and double patenting rejection below).
Claim Interpretation
Claims are interpreted in accordance with the broadest reasonable interpretation (BRI) standard
consistent with the specification (See MPEP 2111). Claims 1, 11, 13, and 14 are interpreted as follows:
The claims and specification did not provide an explicit definition as to the term “kit”. To apply BRI, the term “kit” is interpreted to encompass a collection, set of components or containers.
The term “plurality of oligonucleotides” did not provide an explicit definition in the claims and specification. To apply BRI, the term “plurality of oligonucleotides” is interpreted to encompass plurality of probes, plurality of nucleic acid molecules, or plurality of nucleotides.
Abstract
The abstract of the disclosure is objected to because the abstract should be in narrative form and
generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length.
The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details. The current submitted abstract is 36 words. Examiner requests to bring in a general compound structure to satisfy the abstract requirement.
Correction is required. See MPEP § 608.01(b).
Drawings
New corrected drawings in compliance with 37 CFR 1.121(d) are required in this application because:
The lines, numbers and lettering are not clean, well-defined, sufficiently dense and dark, and uniformly thick and well defined in Figure(s) 9C, 9E, 10, and 11. See 37 CFR 1.84(l) and (q).
Applicant is advised to employ the services of a competent patent draftsperson outside the Office, as the U.S. Patent and Trademark Office no longer prepares new drawings. The corrected drawings are required in reply to the Office action to avoid abandonment of the application. The requirement for corrected drawings will not be held in abeyance.
Specification
The disclosure is objected to because of the following informalities:
The use of a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore, the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
See page 25 and FIG. 19.
Appropriate correction is required.
Claim Objections
Claim 13 is objected to because of the following informalities:
Although the point of attachment can be inferred from the lack of saturation in the succinimide moiety, the specific point of connection is not explicitly shown in the drawing and should be clearly depicted.
Appropriate correction is required.
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.
The factual inquiries 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.
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 1, 13, and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Cai et al. (WO 2014/182528 A2, pub’d 11/13/2014), in view of Stupi et al. (US 2013/0122489 A1, pub’d 05/16/2013).
Cai teaches that a kit comprising a plurality of oligonucleotides designed to adjacent regions of a target nucleic acid (paragraph [0016], and claim 1) and such oligonucleotides are used together as components of a probe system, as required the kit at instant claim 1. Cai further teaches that first plurality of oligonucleotides targeting a first transcript or DNA locus and labeled with a first detectable moiety (claim 1). Cai continually teaches that (1) a detectable moiety comprises a fluorophore (paragraph [0069]); (2) labels include but are not limited to Alexa Fluor family of fluorescent dyes (paragraph [0075]); (3) different fluorophores are employed depending on desired optical properties, sensitivity and assay configuration, and discloses multifuel classes of dye compounds suitable for oligonucleotides (paraphrase [0075] – [0079]).
Cai fails to teach the exact chemical formulas in the instant claims 1, 13, and 14.
Stupi teaches specific structures of fluorophore compounds suitable for attachment to nucleotides and oligonucleotides used in nucleic acid sequencing and detection, as required instant claims 1 (in part, i.e., four of the five structures), and 14 (paragraph [0063], [0067], [0319], [0320] and claims 49-56).
Stupi fail to teach the fifth fluorophore compound recited in instant claim 1, and the structure of claim 13. However, Stupi teaches the structure of Alexa Fluor 594 (paragraph [0063]), which is substantially similar in the fifth fluorophore compound, and the fifth fluorophore structure is predictable substituent modification of Alexa Fluor 594.
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The fifth compound (Instant claim 1) Alexa Fluor 594 from Stupi
Stupi further teaches synthesis of dye labeled 5-[(S)-1-(5-methoxy-2-nitrophenyl)-2,2-dimethyl-propyloxy]methyl-2'deoxycytidine-5'-triphosphate which was employed Alexa Fluor 647. is the same compound as instant claim 13 (paragraph [0166]).
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Alexa Fluor 647 (Instant claim 13) Alexa Fluor 647 labeled compound from Stupi
These specific chemical structures correspond to known species within dye classes, which were widely used fluorophore compounds available to those skilled in the art for labeling oligonucleotides. It would have been obvious to a PHOSITA at the time of the invention to select, modify, and incorporate any one of these known fluorophore structures. The particular chemical formulas recited in claims 1, 13, and 14 does not impact a new function or unexpected technical effect, but instead represents a predictable variation of known dye chemistries selected to achieve expected optical performance characteristics.
The combination of these references is directed to the same field of endeavor and address related to the application of known formulation technique to a known drug substance to obtain a predictable improvement in performance. The Supreme Court in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007) identified a number of rationales to support a conclusion of obviousness which are consistent with the proper "functional approach" to the determination of obviousness as laid down in Graham.
Examples of rationales that may support a conclusion of obviousness include:
(A) Combining prior art elements according to known methods to yield predictable results;
(B) Simple substitution of one known element for another to obtain predictable results;
(C) Use of known technique to improve similar devices (methods, or products) in the same way;
(D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results;
(E) "Obvious to try" – choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success;
(F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art;
(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
Applying KSR example rationale (B), it would have been prima facie obvious to substitute one known fluorophore structure taught by Stupi with another known fluorophore structure to obtain predictable optical results when incorporated into the oligonucleotide probe system of Cai. (see MPEP 2141)
Claims 1, and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Cai et al. (WO 2014/182528 A2, pub’d 11/13/2014), in view of Church et al. (US 2008/0269068 A1, pub’d 10/30/2008).
Cai teaches that a kit comprising a plurality of oligonucleotides designed to adjacent regions of a target nucleic acid (paragraph [0016], and claim 1), and such oligonucleotides are used together as components of a probe system, as mentioned above. Cai further teaches that (1) first plurality of oligonucleotides targeting a first transcript or DNA locus and binding a target nucleic acid via complementary hybridization (paragraph [0007], and claim 2); (2) a second oligonucleotide targeting a second transcript or DNA locus and labeled with a second detectable moiety (claim 2, and 15); (3) probe contain tag sequence complementary to determines detected via fluorescent labeling and hybridization to complementary tag sequences (paragraph [00112], [00151], claim 20, and 21).
Cai fail to teach that (1) at least 12 nucleotides and is capable of binding a target nucleic acid; (2) barcode domain comprises a synthetic backbone; (3) each of the at least four attachment positions have a different nucleic acid sequence.
Church teaches that (1) molecular inversion probe (MIP) comprising oligonucleotide sequences having one or more barcode sequences, one or more guide sequences that are complementary to a specific position on a template target and thus hybridize with the target and one or more tags that are complementary to query nucleic acid sequences (paragraph [0063], and claim 1); (2) target sequences in the range of from 8 to 40 nucleotides and is capable of binding a target nucleic acid (paragraph [0043]); (3) nucleosides includes synthetic nucleosides (paragraph [0046]); (4) the barcode sequences are located in one or more regions of the MIP ((paragraph [0021]); the probe is read by hybridization using complementary oligonucleotides (paragraph [0063], and claim 4); (5) “four contiguous” tag sequences by multiple hybridization imaging cycles, thereby teaching at least four distinct sequence positions in barcode region that are interrogated by complementary nucleic acid molecules (paragraph [0019], [0083], claim 11, and 16).
Accordingly, Cai in view of Church teaches a kit further comprising at least a second plurality of oligonucleotides comparing a target binding domain capable of binding a target nucleic acid and a barcode domain on a synthetic probe backbone having multiple sequence positions that are each capable of being bound by complementary nucleic acid molecules, wherein the sequences at such positions provide an encoded identify for the target and can be used to determine the identity of the target nucleic acid and the nucleotide identity at a queried position. It would have been obvious to a PHOSITA at the time of the invention to incorporate the barcode or tag structure and fluorescent readout into the oligonucleotide probe kit taught by Cai and Church.
Applying KSR example rationale (A), it would have been prima facie obvious to combine the known direct to hybridization based nucleic acid detection using target binding domains and sequence barcode domains read by complementary probes with fluorescent labeling, and such combination shows a predictable use or results, rending the claim obvious to one of ordinary skill in the art at the time of the invention. (see MPEP 2141)
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, 11, 13, and 14 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-16 of U.S. Patent No. 11,821,026 B2 (Dunaway et al., hereinafter “Dunaway I”), in view of Stupi et al. (US 2013/0122489 A1, pub’d 05/16/2013).
The claims of the Dunaway I recite (1) probes comprising a plurality of the probe; (2) a target binding domain and a barcode domain; (3) barcode domain comprising at least four attachment positions; (4) each attachment position comprising at least one attachment region; (5) a barcode domain comprises a single-stranded DNA that is open synthesized in labs as synthetic DNA; (6) attachment region comprising at least one nucleic acid sequence capable of being bound by a complementary nucleic acid molecule; (7) at least four attachment positions correspond to the sequence of the target binding domain; (8) nucleic acid sequences of each position of the at least four attachment positions determine the identity of the target nucleic acid that is bound by said target binding domain one nucleotide in said target nucleic acid that is bound by said target binding domain.
In the limitations in instant claim 11, a kit comprises at least a second plurality of oligonucleotides is an obvious implementation of the plurality of probes, and “at least 12 nucleotides” and “at least four attachments” applies the same encoding principle taught by Dunaway, and does not provide a new or unexpected result.
The claims of Dunaway I fail to teach that a specific probe as required by claims.
However, Stupi teaches the specific fluorophore and its attachment to DNA (paragraph [0063], [0067], [0319], [0320] and claims 49-56), as previously mentioned.
Applying KSR example rationale (B), it would have been obvious to substitute one dye for another. One would predict that the probes would maintain their function.
Claims 1, 11, 13, and 14 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-19 of U.S. Patent No. 12,281,356 B2 (Dunaway et al., hereinafter “Dunaway II”), in view of Stupi et al. (US 2013/0122489 A1, pub’d 05/16/2013).
The claims of the Dunaway II teaches (1) a target binding domain and a barcode domain; (2) barcode domain comprising at least four attachment positions; (3) each attachment position comprising at least one attachment region; (4) synthetic backbone comprises L-DNA; (5) attachment region comprising at least one nucleic acid sequence capable of being bound by a complementary nucleic acid molecule; (6) at least four attachment positions correspond to the sequence of the target binding domain; (7) nucleic acid sequences of each position of the at least four attachment positions determine the identity of the target nucleic acid that is bound by said target binding domain one nucleotide in said target nucleic acid that is bound by said target binding domain.
In the limitations in instant claim 11, a kit comprises at least a second plurality of oligonucleotides is an obvious implementation of the plurality of probes from several different attachment position.
The claims of Dunaway II fails to teach that a specific probe as required by claims.
However, Stupi teaches the specific fluorophore and its attachment to DNA (paragraph [0063], [0067], [0319], [0320] and claims 49-56), as previously mentioned.
Applying KSR example rationale (B), it would have been obvious to substitute one dye for another. One would predict that the probes would maintain their function.
Claims 1, 11, 13, and 14 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 77-99 of copending Application No. 18/985,839 (Dunaway et al., hereinafter “Dunaway III”), in view of Stupi et al. (US 2013/0122489 A1, pub’d 05/16/2013).
This is a provisional nonstatutory double patenting rejection.
Regarding instant claims, claim 77 of Dunaway III teaches (1) a target binding domain and a barcode domain; (2) barcode domain comprising at least four attachment positions; (3) each attachment position comprising at least one attachment region; (4) attachment region comprising at least one nucleic acid sequence capable of being bound by a complementary nucleic acid molecule; (5) at least four attachment positions correspond to the sequence of the target binding domain. Dunaway III further teaches (3) barcode domain comprises a synthetic backbone (claim 78); (2) at least 12 nucleotides and is capable of binding a target nucleic acid (claims 83, and 84); (3) nucleic acid sequences of each position of the at least four attachment positions determine the identity of the target nucleic acid that is bound by said target binding domain one nucleotide in said target nucleic acid that is bound by said target binding domain (claims 77, 92, 97, and 99).
The distinction between a “kit” in instant claim 11 and a “set of probes” in Dunaway III claim 77 represents a difference in claim form or terminology. Both claims encompass a collection of nucleic acid probes intended for use together, and expressional differences do not confer patentable distinction. Further, the number of “at least three attachment positions” in claim 77 and “at least four attachments” in instant claim 11 applies the same encoding principle, and does not provide a new fundamental structure or unexpected result.
Dunaway III fails to teach that a specific probe as required by claims.
However, Stupi teaches the specific fluorophore and its attachment to DNA (paragraph [0063], [0067], [0319], [0320] and claims 49-56), as previously mentioned.
Applying KSR example rationale (B), it would have been obvious to substitute one dye for another. One would predict that the probes would maintain their function.
Conclusion
Claims 1, 11, 13, and 14 are rejected.
Claim 13 is objected to.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SEONG JONG KIM whose telephone number is (571)272-6918. The examiner can normally be reached 7:00am-3:30pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Clinton A. Brooks can be reached at 571-270-7682. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SEONG JONG KIM/Examiner, Art Unit 1621
/CLINTON A BROOKS/Supervisory Patent Examiner, Art Unit 1621