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 .
DETAILED ACTION
This Non-Final Office Action is responsive to the communication received 11/20/2025.
Election/Restrictions
Applicant’s election without traverse in the Reply filed on 11/20/2025 of Group I, Claim(s) 1-17 is acknowledged. Applicant has elected in the Reply filed on 11/20/2025 the following species:
A. the blocking oligonucleotide comprises (b) a sequence that is reverse complementary to the second end sequence but does not comprise a sequence of more than 3 contiguous nucleotides reverse complementary to the first end sequence, such that the blocking oligonucleotide competes with the linking oligonucleotide for hybridization to the second oligonucleotide, allowing the second oligonucleotide to remain released from the bead (claim 1)
Because applicant did not distinctly and specifically point out the supposed errors in the species election requirement, the election has been treated as an election without traverse (MPEP § 818.03(a)).
The Restriction/Election Requirements are thus deemed proper and are made FINAL.
Claims 1-20 are pending.
Claims 18-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the Reply filed on 11/20/2025.
Claims 1-17 are under examination in this Office Action.
Claim Objections
Claim(s) 14-17 is/are objected to under 37 CFR 1.75(c) as being in improper form because a multiple dependent claims 14, 16 and 17 cannot depend from any other multiple dependent claim. See MPEP § 608.01(n). Accordingly, the claim(s) 14-17 has/have not been further treated on the merits. Claims 15-17 depend directly or indirectly from claim 14.
Claim Rejections - 35 USC § 102
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 1-13 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Mazur et al. (08/05/2021) PCT International Patent Application Publication WO 2021/155371 A1 corresponding to US Patent Application Publication 2023/0062391 A1 (hereinafter referred to as "Mazur").
With regards to claims 1-13, Mazur teaches:
a) as in claims 1-13, a method of releasing an oligonucleotide from a bead, the method comprising, (i) providing a reaction mixture comprising: a plurality of beads, each bead covalently linked to a first oligonucleotide comprising a first end sequence, a second oligonucleotide comprising a second end sequence; and a linking oligonucleotide comprising (i) a first terminal sequence that is reverse complementary to the first end sequence and (ii) a second terminal sequence that is reverse complementary to the second end sequence, wherein the first terminal sequence and first end sequence are hybridized and have a first melting temperature (Tm) and (ii) the second terminal sequence and second end sequence are hybridized and have a second Tm such that the linking oligonucleotide links the first oligonucleotide to the second oligonucleotide; (ii) raising the temperature of the reaction mixture higher than at least one of the first and second Tm such that the first oligonucleotide and the second oligonucleotide are disassociated from at least one end of the linking oligonucleotide; (iii) lowering the temperature of the reaction mixture below the first and second Tm, wherein after the raising and before the lowering the reaction mixture further comprises a blocking oligonucleotide comprising either: (a) a sequence that is reverse complementary to the first end sequence but does not comprise a sequence of more than 3 contiguous nucleotides reverse complementary to the second end sequence, such that the blocking oligonucleotide competes with the linking oligonucleotide for hybridization to the first oligonucleotide, allowing the second oligonucleotide to remain released from the bead, or (b) a sequence that is reverse complementary to the second end sequence but does not comprise a sequence of more than 3 contiguous nucleotides reverse complementary to the first end sequence, such that the blocking oligonucleotide competes with the linking oligonucleotide for hybridization to the second oligonucleotide, allowing the second oligonucleotide to remain released from the bead or (c) a sequence that is the first end sequence but does not comprise a sequence of more than 3 contiguous nucleotides in the second end sequence, such that the blocking oligonucleotide competes with the linking oligonucleotide for hybridization to the first oligonucleotide, allowing the second oligonucleotide to remain released from the bead, or (d) a sequence that is the second end sequence but does not comprise a sequence of more than 3 contiguous nucleotides that is the first end sequence, such that the blocking oligonucleotide competes with the linking oligonucleotide for hybridization to the second oligonucleotide, allowing the second oligonucleotide to remain released from the bead; wherein the first end sequence is a 3′ end sequence; wherein the first end sequence is a 5′ end sequence; wherein the second oligonucleotide has a barcode sequence, wherein individual beads comprise clonal copies of the second oligonucleotide and wherein the barcode sequence for individual beads are unique such that the barcode distinguishes the bead from other beads in the plurality; wherein the 3′ end of the second oligonucleotide comprises a target-specific sequence; wherein the 3′ end of the second oligonucleotide comprises a universal tag sequence; wherein the 3′ end of the second oligonucleotide comprises at least 4 contiguous thymines; wherein the providing (i) comprises forming a mixture of beads, wherein each bead is covalently linked to a long oligonucleotide comprising the first oligonucleotide and the second oligonucleotide, wherein the first end sequence of the first oligonucleotide is linked directly, or indirectly via a linker sequence, to the second end sequence of the second oligonucleotide, and wherein long oligonucleotides on different beads are distinguishable by a different barcode sequence in the long oligonucleotide; and hybridizing the linking oligonucleotide to the long oligonucleotide such that the first terminal sequence is hybridized to the first end sequence and the second terminal sequence is hybridized to the second end sequence; and cleaving the long oligonucleotide between the first end sequence and the second end sequence while the linking oligonucleotide remains intact and links the first oligonucleotide to the second oligonucleotide; wherein the linker sequence comprises one or more uracil nucleotide and the cleaving comprises contacting the long oligonucleotide with uracil DNA glycosylase and endonuclease VIII, thereby excising the one or more uracil; wherein the linker sequence comprises one or more ribonucleotide and the cleaving comprises cleaving the linker sequence in a ribonucleotide-specific manner using RNAseH; wherein a restriction site is located between the first oligonucleotide and the second oligonucleotide and the cleaving comprises contacting the long oligonucleotide with a restriction enzyme that cleaves the restriction site on the long oligonucleotide without cleaving the linking oligonucleotide using a nicking endonuclease; wherein the blocking oligonucleotide is added to the reaction mixture following the cleaving of the long oligonucleotide between the first end sequence and the second end sequence; wherein the concentration of the blocking oligonucleotide in the reaction mixture is higher than the concentration of the linker oligonucleotide in the reaction mixture (see Figures 6A and 6B and [0369] to [0503]).
Thus, Mazur anticipates the present claims.
Conclusion
No claim is allowed.
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/CHRISTIAN C BOESEN/Primary Examiner, Art Unit 1684