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 Application
Claim(s) 58-66 and 76 are pending and under examination
Claim(s) 67-75 are withdrawn from consideration.
Applicant’s election without traverse of Group I, which includes Claims 58-66 and 76 in the reply filed on 02/04/2026 is acknowledged. Claim(s) 67-75 withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected method for using a stem loop primer, there being no allowable generic or linking claim.
Claim Objections
Claim 61 objected to because of the following informalities: “Tm” acronyms or abbreviated terms should be spelled out fully upon their first appearance in the claims and can then later be shortened. Appropriate correction is required.
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.
Claim(s) 58-60, 62-65 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Glezer et al. (US20210198730A1, EFD: December 31st 2019).
Regarding claim 58-60 and 76, Glezer discloses oligonucleotides, comprising: a 5′ arm sequence configured to hybridize to a first end region of a polynucleotide sequence; a stem-loop sequence containing a unique molecular identifier (UMI); and a 3′ arm sequence configured to hybridize to a second end region of said polynucleotide sequence, wherein said stem-loop sequence comprises: a 5′ stem sequence; a loop sequence containing said UMI; and a 3′ stem sequence [Fig 1A, shown below.].
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Regarding claim 62, Glezer discloses 3′ and 5′ arm sequence/hybridization pad comprises 5-22, 5-10, or 20-22 nucleotides in length (e.g. hybridization pad includes about 5 to about 15 nucleotides [¶0054])
Regarding claim 63, Glezer discloses stem sequences are 5-22, 5-10, or 20-22 nucleotides in length. (e.g. the stem includes about 5 to about 10 nucleotides [¶0055]).
Regarding claim 64, Glezer discloses loop sequence is 6-20 nucleotides in length. (e.g. the loop includes about 10 to about 20 nucleotides [¶0056]).
Regarding claim 65, Glezer discloses oligonucleotide primer comprises a terminal hydrophobic group. (e.g. In embodiments, the hybridization pad includes one or more modified nucleotides [¶0077], wherein “modified nucleotide” can include a blocking moiety (to prevent further extension) such as phenylthiomethyl group [¶0041])
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.
Glezer et al.
Claim(s) 61 is/are rejected under 35 U.S.C. 103 as being unpatentable over Glezer et al. (US20210198730A1, EFD: December 31st 2019).
Regarding claim 61, Glezer discloses stem region is stable at approximately 37° C, and denatures at temperatures greater than 50° C [¶0055], while target hybridization pads denature at temperatures greater than 40-45° C [¶0077]. Glezer further discloses relative short hybridization pad sequences and expressly recognize that pad sequences can be adjusted through sequence selection and modified nucleotides [¶0077, 0164, 0179, 0187, 0197]. Althogh Glezer does not explicitly disclose the 3′ and 5′ arm sequences have a lower Tm than stem sequences, it would have been prima facie obvious to a person of ordinary skill in the art to select pad sequences to have a lower Tm, e.g. the disclosed 40-45° C rage, than the stem region, e.g. above 50° C, so that upon thermal disassociation between the target and oligonucleotide probe, the stem remains hybridize, preserving the stem-loop structure and allowing the probes to be available for subsequent rounds of target hybridization and processing. See MPEP § 2144.05 (II) "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)
Glezer et al. and Raz et al.
Claim(s) 66 is/are rejected under 35 U.S.C. 103 as being unpatentable over Glezer et al. (US20210198730A1, EFD: December 31st 2019) in view of Raz et al. (US20180274029A1, EFD: March 24th 2018).
Regarding claim 66, Glezer disclose primer comprise biotinylated loop region instead of biotinylated terminal [¶0056].
Raz discloses the 5′ end of the universal hairpin primer can include one or more labels such as biotin/streptavidin or a fluorophore, such as a donor molecule (fluorescein) and an acceptor molecule (DABCYL) [¶0075].
As of the application’ s effective filing date, it would have been prima facie obvious to a person of ordinary skill in the art to place biotin group at 5′ end of the universal hairpin primer, per Raz teaching, in Glezer’s primer design to avoid introducing bulky label within the functional barcode loop region while retaining the biotin label on the primer. Such design is advantageous for downstream target enrichment, amplification, and sequencing of the barcode section within the loop. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, USPQ2d 1385, 1395 — 97 (2007) (MPEP § 2143).
Conclusion
No claims are allowed
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Khai Quynh Tien Pham whose telephone number is (571)272-6998. The examiner can normally be reached M-T, 9-4 ET.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Heather Calamita can be reached at (571) 272-2876. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KHAI QUYNH TIEN PHAM/ Examiner, Art Unit 1684
/JEREMY C FLINDERS/ Primary Examiner, Art Unit 1684
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