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 .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 11/17/23, 3/25/26, 5/1/26 is being considered by the examiner.
Claim Status
Claims 70-89 are pending and are examined.
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 70-80 and 85 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Hindson (US Pub 2014/0378345).
Regarding Claim 70, Hindson teaches a method for providing an array ([0268] devices for making beads and for combining beads (or other types of partitions) with samples, e.g., for co-partitioning sample components and beads. [0166] barcodes or partial barcodes may be generated from oligonucleotides obtained from or suitable for use in an oligonucleotide array, such as a microarray or bead array.), comprising:
(a) partitioning a plurality of Round 1 beads into wells on a substrate, wherein the Round 1 bead in a first well and the Round 1 bead in a second well each comprises a different Round 1 oligonucleotide ([0460] Functionalized beads are produced by partitioning in wells according to the method illustrated in FIGS. 13A and 13B. The first functionalization step is outlined in FIG. 13A, the second functionalization step is outlined in FIG. 13B. An example multiplex adaptor creation scheme is outlined in FIG. 13C and described in Example 11. As shown in FIG. 13A, functionalized beads, 1301 (e.g., beads with acrydite oligos and primer (e.g., 5'-AAUGAUACGGCGACCACCGAGA-3'), the template with barcode sequence, 1302 (e.g., 5'-TCTCGGTGGTCGCCGTATCATT-3'), and appropriate PCR reagents, 1303, are mixed together, 1304/1305 and divided into 384 wells of a multi-well plate. Each well comprises multiple copies of a unique barcode sequence and multiple beads.);
(b) disrupting the Round 1 beads to release the Round 1 oligonucleotides, wherein the released Round 1 oligonucleotides are attached to nucleic acid molecules in the corresponding well via ligation to generate extended nucleic acid molecules ([0098] disrupting the barcoded beads, and/or disrupting the linkage to attached sequences, thereby releasing the attached barcode sequences from the bead. The barcode sequences may be released either by degrading the bead, detaching the oligonucleotides from the bead such as by a cleavage reaction, or a combination of both. [0009] The first partitions may by co-partitioned with components of a sample material into a plurality of second partitions. The barcode molecules can be released from the first partitions into the second partitions. The released barcode molecules can then be attached to the components of the sample material within the second partitions.);
(c) partitioning a plurality of Round 2 beads into wells on the substrate, wherein the Round 2 bead in the first well and the Round 2 bead in the second well each comprises a different Round 2 oligonucleotide ([0460] Functionalized beads are produced by partitioning in wells according to the method illustrated in FIGS. 13A and 13B. The first functionalization step is outlined in FIG. 13A, the second functionalization step is outlined in FIG. 13B. An example multiplex adaptor creation scheme is outlined in FIG. 13C and described in Example 11. As shown in FIG. 13A, functionalized beads, 1301 (e.g., beads with acrydite oligos and primer (e.g., 5'-AAUGAUACGGCGACCACCGAGA-3'), the template with barcode sequence, 1302 (e.g., 5'-TCTCGGTGGTCGCCGTATCATT-3'), and appropriate PCR reagents, 1303, are mixed together, 1304/1305 and divided into 384 wells of a multi-well plate. Each well comprises multiple copies of a unique barcode sequence and multiple beads. [0201] For example, separate populations of beads may be provided to which barcode containing oligonucleotides are to be attached.); and
(d) disrupting the Round 2 beads to release the Round 2 oligonucleotides, wherein the released Round 2 oligonucleotides are attached to the extended nucleic acid molecules in the corresponding well via ligation to generate further extended nucleic acid molecules ([0012] In some cases, the composition comprises a plurality of first partitions and a plurality of different second partitions. Each of the different second partitions can be disposed within a separate first partition and may comprise a plurality of oligonucleotides releasably associated therewith. In some cases, the different second partitions may comprise at least 1,000 different second partitions, at least 10,000 different second partitions. [0201] In some combinatorial approaches, ligation methods may be used to assemble oligonucleotide sequences comprising barcode sequences on beads (e.g., degradable beads as described elsewhere herein).
Regarding Claim 71, Hindson teaches the method of claim 70, wherein the Round 2 oligonucleotides are at least four nucleotides in length ([0017] the identical barcode sequence may be between about 6 nucleotides and about 20 nucleotides in length.).
Regarding Claim 72, Hindson teaches the method of claim 70, wherein the released Round 2 oligonucleotides in the first and second wells comprise a first and second Round 2 barcode sequence, respectively, wherein the first and second Round 2 barcode sequences are different from each other ([0012] The oligonucleotides associated with each second partition can comprise a common barcode sequence and the oligonucleotides associated with different second partitions can comprise different barcode sequences.)
Regarding Claim 73, Hindson teaches the method of claim 70, wherein the released Round 2 oligonucleotide comprises a sequence that hybridizes to a Round 2 splint which in turn hybridizes to the extended nucleic acid molecules in a particular well, and wherein the released Round 2 oligonucleotide is ligated to the extended nucleic acid molecules using the Round 2 splint as a template to generate the further extended nucleic acid molecules ([0203] the first oligonucleotide may be attached to the separate populations with the aid of a splint (an example of a splint is shown as 2306 in FIG. 23A. [0204] a splint may be configured such that it comprises the first oligonucleotide or oligonucleotide segment hybridized to an oligonucleotide that comprises a sequence that is in part complementary to at least a portion of the first oligonucleotide or oligonucleotide segment and a sequence (e.g., an overhang sequence) that is in part complementary to at least a portion of an oligonucleotide attached to the separate populations. The splint can hybridize to the oligonucleotide attached to the separate populations via its complementary sequence. Once hybridized, the first oligonucleotide or oligonucleotide segment of the splint can then be attached to the oligonucleotide attached to the separate populations via any suitable attachment mechanism, such as, for example, a ligation reaction.).
Regarding Claim 74, Hindson teaches the method of claim 70, wherein the released Round 1 oligonucleotides each individually comprises a sequence that hybridizes to a Round 1 splint which in turn hybridizes to the nucleic acid molecules in a particular well, and wherein the released Round 1 oligonucleotides are ligated to the nucleic acid molecules using the Round 1 splint as a template to generate the extended nucleic acid molecules ([0203] the first oligonucleotide may be attached to the separate populations with the aid of a splint (an example of a splint is shown as 2306 in FIG. 23A. [0204] a splint may be configured such that it comprises the first oligonucleotide or oligonucleotide segment hybridized to an oligonucleotide that comprises a sequence that is in part complementary to at least a portion of the first oligonucleotide or oligonucleotide segment and a sequence (e.g., an overhang sequence) that is in part complementary to at least a portion of an oligonucleotide attached to the separate populations. The splint can hybridize to the oligonucleotide attached to the separate populations via its complementary sequence. Once hybridized, the first oligonucleotide or oligonucleotide segment of the splint can then be attached to the oligonucleotide attached to the separate populations via any suitable attachment mechanism, such as, for example, a ligation reaction.).
Regarding Claim 75, Hindson teaches the method of claim 74 wherein the Round 1 splint is comprised in the Round 1 bead and released upon disruption of the bead ([0213] As shown in FIG. 23B, beads 2301 can be added to each well of the plate and the splint 2306 in each well can hybridize with the corresponding anchor sequence. Following ligation, the products can be pooled and the beads washed to remove unligated oligonucleotides.).
Regarding Claim 76, Hindson teaches the method of claim 73, wherein the Round 2 splint is common between different wells ([0220] Such products can be generated by hybridizing the first component of the desired sequence (e.g., sequence 2502 in FIG. 25 comprising a first partial barcode sequence; the first component may also be attached to a bead) with the overhang common to each splint (e.g., overhang 2609 in FIG. 26).
Regarding Claim 77, Hindson teaches the method of claim 73, wherein the Round 2 splint is comprised in the Round 2 bead and released upon disruption of the Round 2 bead ([0206] the second oligonucleotide may be attached to the first oligonucleotide with the aid of a splint. For example, the splint used to attach the first oligonucleotide or oligonucleotide segment to the separate populations prior to generating the mixed pooled population may also comprise a sequence (e.g., an overhang sequence) that is in part complementary to at least a portion of the second oligonucleotide. The splint can hybridize to the second oligonucleotide via the complementary sequence. Once hybridized, the second oligonucleotide can then be attached to the first oligonucleotide via any suitable attachment mechanism, such as, for example, a ligation reaction. The splint strand complementary to both the first and second oligonucleotides can then be then denatured (or removed) with further processing. [0375] The targeted barcode constructs may be released from the bead (e.g., via degradation of the bead--for example, via a reducing agent in cases where the bead is a gel bead comprising disulfide bonds) in the partition and allowed to prime their target sequence on their respective strand (e.g., forward strand or reverse strand) of sample nucleic acid.).
Regarding Claim 78, Hindson teaches the method of claim 73, wherein the Round 2 splint is not comprised in the Round 2 bead and is separately delivered to the wells ([0214] As shown in FIG. 23C, the washed products can then be redistributed into wells of another plate (e.g., a 384-well plate), with each well of the plate comprising an oligonucleotide 2305 that has a unique second partial barcode sequence).
Regarding Claim 79, Hindson teaches the method of claim 70, wherein the released Round 2 oligonucleotide comprises a sequence that hybridizes to a Round 3 splint which in turn hybridizes to a Round 3 oligonucleotide, and wherein the Round 3 oligonucleotide is ligated to the further extended nucleic acid molecules using the Round 3 splint as template to generate even further extended nucleic acid molecules ([0211] As noted previously, either or both of the first and second oligonucleotide sequences or sequence segments, or subsequently added oligonucleotides (e.g., addition of a third oligonucleotide to the second oligonucleotide, addition of a fourth oligonucleotide to an added third oligonucleotide, etc.), may include additional sequences).
Regarding Claim 80, Hindson teaches the method of claim 70, wherein the Round 1 oligonucleotide and/or the Round 2 oligonucleotide each comprises a capture sequence ([217] in FIG. 23, the determined overhang 2506 may be used to capture sequence 2502 (which may be attached to a bead as shown in FIG. 23)
Regarding Claim 85, Hindson teaches the method of claim 80, wherein the Round 1 oligonucleotide and the Round 2 oligonucleotide each comprises a different capture sequence, wherein each capture sequence is designed to couple to one or more analytes ([0177] In some cases, oligonucleotides with different sequences (or the same sequences) are attached to the beads in separate steps.).
Claim Rejections - 35 USC § 103
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.
Claims 81, 82, 83, and 84 are rejected under 35 U.S.C. 103 as being unpatentable over Hindson (US Pub 2014/0378345), in view of Banyai (US Pub 2015/0038373).
Regarding Claims 81, 82, 83, and 84, Horgan teaches the method of claim 70.
Hindson is silent to prior to the partitioning in step (a), the substrate is coated with a photoresist layer, prior to the partitioning in step (a), the substrate is coated with a photoresist layer by dipping or spin coating, wells are formed by etching a layer of a photoresist on the substrate, comprising removing the photoresist, leaving the further extended nucleic acid molecules immobilized on the substrate.
Banyai teaches in the related art of nucleic acids. [0237] Photoresist typically refers to a light-sensitive material commonly used in standard industrial processes, such as photolithography, to form patterned coatings. It is applied as a liquid, but it solidifies on the substrate as volatile solvents in the mixture evaporate. It may be applied in a spin coating process as a thin film (1 um to 100 um) to a planar substrate. It may be patterned by exposing it to light through a mask or reticle, changing its dissolution rate in a developer. It may be used as a sacrificial layer that serves as a blocking layer for subsequent steps that modify the underlying substrate (such as etching). Once that modification is complete, the resist is removed. [0238] Photolithography may refer to a process for patterning substrates. [0245] Sixth, the resist may be stripped and removed, for example by dissolving it in suitable organic solvents, plasma etching, exposure and development, etc., thereby exposing the areas of the substrate that had been covered by the resist. In some embodiments, a method that will not remove functionalization groups or otherwise damage the functionalized surfaces is selected for the resist strip.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have added the steps of partitioning in step (a), the substrate is coated with a photoresist layer, prior to the partitioning in step (a), the substrate is coated with a photoresist layer by dipping or spin coating, wells are formed by etching a layer of a photoresist on the substrate, comprising removing the photoresist, leaving the further extended nucleic acid molecules immobilized on the substrate, as taught by Banyai, to the method, as taught by Hindson, to allow for using photoresist are employed wherein photoresist facilitates manufacturing of substrates with differential functionalization, as taught by Banyai, in [0239].
Claims 86, 87, 88, and 89 are rejected under 35 U.S.C. 103 as being unpatentable over Hindson (US Pub 2014/0378345), in view of Lauks (US Pub 2003/0127333).
Regarding Claims 86, 87, 88, and 89, Horgan teaches the method of claim 70.
Hindson is silent to the further extended nucleic acid molecules migrate into a porous material abutting the wells, the porous material is a gel and the migration comprises electrophoresis, the migration paths in the porous material are substantially parallel to one another, and the porous material is divided into subparts along one or more planes intersecting the migration paths, thereby generating copies of the array, the porous material is divided into subparts along one or more planes that are substantially perpendicular to the mean migration direction.
Lauks teaches in the related art of DNA micro-arrays in [0005]. [0022] Yet another approach to parallel experimentation is the collection of methods known as solid-phase reaction formats. In these methods reactions are performed on planar slabs of porous or gelatinous materials. Devices of this art include nucleic acid arrays on porous substrates and gels such as those used in traditional blotting techniques, multi-lane gel slabs for parallel electrophoresis separations can be classified as solid phase reactions. In the continuous format approach, sample is spotted onto a planar porous slab that is laminated with one or more other planar slabs containing reaction reagents. At the time of the assay, sample and reagents intermix by diffusion between slabs. Using this approach, the continuous format devices avoid the fluidic i/o complexity of the other array technologies. However, the spot separation is relatively large (several milimeters) because individual reaction micro-locations must be sufficiently well separated to avoid mixing between reaction chemicals of adjacent micro-locations when they diffuse along the planar slab.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have added the steps of further extended nucleic acid molecules migrate into a porous material abutting the wells, the porous material is a gel and the migration comprises electrophoresis, the migration paths in the porous material are substantially parallel to one another, and the porous material is divided into subparts along one or more planes intersecting the migration paths, thereby generating copies of the array, the porous material is divided into subparts along one or more planes that are substantially perpendicular to the mean migration direction, as taught by Lauks, to the method of Hindson, to allow for parallel experimentation, as taught by Lauks, in [0022].
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JACQUELINE BRAZIN whose telephone number is (571)270-1457. The examiner can normally be reached M-F 8-5.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Charles Capozzi can be reached at 571-270-3638. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JB/
/CHARLES CAPOZZI/Supervisory Patent Examiner, Art Unit 1798
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