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 .
Election/Restrictions
Applicant’s election of Group I: Claims 1-13 in the reply filed on 08/05/2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)). Claims 14-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to non-elected Groups II-III.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 12-13 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 12 and 13 depend from Claim 11, which recites that “each of the independently removable coatings is a photo-cleavable protective layer”. However, Claims 12 and 13 recite both photo-cleavable groups for breaking down the layer, as well as acid-labile groups for breaking down the layer, wherein acid-labile-type groups are not necessarily photo-cleavable.
Applicant’s instant specification paras. [0163-0164] describe the acid-labile embodiments as light-responsive when used with a photoacid generator; however, Claims 12 and 13 do not require the photoacid generator necessary for the acid-labile group to be cleaved in a photo-induced manner. As such, the claim is indefinite for broadening the scope to non-photo-cleavable acid-labile groups as it is unclear how these groups satisfy the photo-cleavable condition of Claim 11 and, at present, refer to acid-labile groups not requiring photo-induced cleavage as required by Claim 11.
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.
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 1-8 and 10 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ramirez et al. (US 2018/0327832 A1), hereinafter “Ramirez”.
Regarding Claim 1, Ramirez teaches a flow cell ([0038-0039]), comprising:
a substrate 12 ([0190[: “The flow cell 10 includes the patterned substrate 12, which may be a die...or a wafer...”);
a plurality of reactive regions spatially separated from one another across the substrate 12 (See para. [0040] and Fig. 5L showing reactive regions formed by reactive groups 22 being spaced apart by the interstitial regions 16.), each of the plurality of reactive regions including:
a polymeric hydrogel layer 20 (See Fig. 5L showing the hydrogel 20 comprised in the reactive region supporting the reactive primers 22, [0104]: “The functionalized polymer coating layer may be a hydrogel...”, and [0191]: “The surface chemistry includes the functionalized polymer coating layer 20 and the primers 22.”); and
a reactive entity 22 attached to the polymeric hydrogel layer 20 (See Fig. 5L showing the primers 22 on the hydrogel 20, and [0038]: “a functionalized polymer coating layer and a primer grafted thereto” wherein primers are reactive entities which undergo binding reactions, cleavage, etc.); and
a plurality of independently removable coatings respectively positioned over each of the plurality of reactive regions (See Fig. 3 and [0277]: The example flow cells (1A and 1B) included several flow channels/lanes...where each lane was in fluid communication with a plurality of wells...A PAZAM layer was formed in each well, and 1 μm primers were grafted on the PAZAM layer. Protective coatings were ultimately formed on the surface chemistry...” – As, Ramirez provides independently addressable, isolated flow channels of the flow cell ([0172]) each with respective protective coatings as in para. [0277], each coating positioned over a reactive region (wherein the plurality of wells of each lane in Ramirez may be considered a reactive region as the term “region” is broadly interpreted herein as merely a designated zone of the device having the hydrogel and primers and is not required to be contiguous) each of the plurality of coatings is thereby independently removable.),
as in Claim 1.
Regarding Claim 2, the prior art meets the limitations of Claim 1 as discussed above. Further, Ramirez teaches the flow cell discussed above wherein at least one of the plurality of independently removable coatings has a different removal characteristic than at least one other of the plurality of independently removable coatings (The different removal characteristic being the different locations/channels from which the protective coating is independently removed as discussed above regarding Claim 1.), as in Claim 2.
Regarding Claim 3, the prior art meets the limitations of Claim 2 as discussed above. Further, Ramirez teaches the flow cell discussed above wherein each of the plurality of independently removable coatings has a different removal characteristic than each other of the plurality of independently removable coatings (The different removal characteristic being the different locations/channels from which the protective coating is independently removed as discussed above regarding Claim 1.), as in Claim 3.
Regarding Claim 4, the prior art meets the limitations of Claim 3 as discussed above. Further, Ramirez teaches the flow cell discussed above wherein the removal characteristic is solubility (See [0280]: “Each of the dried protective coatings had a different concentration of the copolymer.” – As the copolymer is what is solubilized by water, and each of the dried coatings has a different concentration (corresponding to amount/thickness when dried) of the copolymer, the solubility among each of the protective layers is different, as it requires more fluid to solubilize a greater amount of polymer into solution. As such, the concentration of dried protective layer directly influences how quickly and how much of said protective layer dissolves, which in turn affects the overall solubility and release profile. – See further [0060] “In some examples of the methods and flow cells described herein, the water-soluble protective coating comprises a water-soluble, non-cationic synthetic polymer; a water-soluble natural polysaccharide or a derivative thereof; a water-soluble natural protein or a derivative thereof; a water-soluble salt; or a water-soluble small molecule compound selected from the group consisting of a water-soluble surfactant, a sugar, an antioxidant, a chelator, a buffer, a glycol, glycerol, and a cyclodextrin; or a combination thereof.”, and [0357]: “Comparative coatings (different water-soluble cationic polymers) were formed on the surface chemistry in five of the eight lanes, and one of the eight lanes was left uncoated.” – Therein, Ramirez expressly teaches of combinations of different water-soluble species as different protective layers in the different channels of the flow cell, each of which having respective solubility characteristics depending on the chemical structure.), as in Claim 4.
Regarding Claim 5, the prior art meets the limitations of Claim 1 as discussed above. Further, Ramirez teaches the flow cell discussed above wherein the reactive entity in each of the plurality of reactive regions is a primer set (See Fig. 5L showing the primers 22 in each of the plurality of reactive regions (depressions in the substrate 12), and para. [0078] discussing primer sets (Primer A and Primer B) and their hybridization/binding with target oligonucleotides, thereby representing the “reactive entity” by undergoing said hybridization/binding reactions.), as in Claim 5.
Regarding Claim 6, the prior art meets the limitations of Claim 5 as discussed above. Further, Ramirez teaches the flow cell discussed above wherein the primer set is the same in each of the plurality of reactive regions (See Figs. 5C and 5D showing the same functionalized layer across each of the depressions of the substrate 12, and para. [0150] discussing spin or dip coating such that the entire surface of the substrate having all the depressions/printed features are filled with the same functionalized polymer. See further Figs. 5D and 5E showing the primers being simultaneously deposited to each of the functionalized polymers, and para. [0155] discussing spin or dip coating such that the entire surface of the substrate having all the functionalized polymer features are exposed to primer at once. By such simultaneous coating, each of the reactive regions must contain the same set of primers, as each region has a functional group complimentary to the simultaneously applied primers. – See also para. [0356] discussing the same primer graft mix being applied across eight lanes of the flow cell -- and Examples 1-3.), as in Claim 6.
Regarding Claim 7, the prior art meets the limitations of Claim 5 as discussed above. Further, Ramirez teaches the flow cell discussed above wherein the primer set of at least one of the plurality of reactive regions is different than the primer set of at least one other of the plurality of reactive regions (Given that the primer sets attached to each of the spatially sequestered functionalized regions 20 (Fig. 3) are separated by the sidewalls 29 and/or the interstitial regions 16, the primer sets of each of the regions is “different” (interpreted broadly herein to encompass spatial separation as a “difference”), as opposed to one contiguous layering of a primer set across the entirety of the substrate. – Applicant may wish to amend the claim to recite that the primer set of at least one of the plurality of reactive regions has a different sequence than the primer set of at least one other of the plurality of reactive regions, so as to specify the intended difference.), as in Claim 7.
Regarding Claim 8, the prior art meets the limitations of Claim 1 as discussed above. Further, Ramirez teaches the flow cell discussed above wherein:
at least one of the plurality of independently removable coatings includes a plurality of sub-layers (The “plurality of sub-layers” is interpreted in accordance with Applicant’s instant specification para. [0154]: “the sub-layers, e.g., coatings 36A, 36B, 36C” and shown in Fig. 2A as being separate, adjacent layers rather than additional laminate-type layers within each protective layer. (However, if this is not the case, see also para. [0237] discussing multiple layered sub-layers of the protective coating (24 and 24’) – Herein, the sub-layers of Ramirez are the separate protective coatings 24, as seen through Fig. 3 which are separate, adjacent, and independently addressable by selection of the desired flow channel.); and
the plurality of sub-layers defines a removal characteristic of the at least one of the plurality of independently removable coatings (As the plurality of sub-layers 24 are spatially separated as seen through Fig. 3, the plurality of sub-layers 24 define a removal characteristic of the coatings given their spatial separation allows them to be independently addressable, thereby having a different removal characteristic in the selection of the channel.), as in Claim 8.
Regarding Claim 10, the prior art meets the limitations of Claim 1 as discussed above. Further, Ramirez teaches the flow cell discussed above wherein each of the plurality of removable coatings has a different thickness (See [0280]: “Each of the dried protective coatings had a different concentration of the copolymer.” – As the flow lanes are identical duplicates, such as seen through Fig. 3, a drying of protective layer fluid in the lane channels having higher concentration will dry to form a thicker layer, and those having the lower concentration will dry to form a thinner layer, merely because when the concentration is higher, there are more molecules to deposit upon drying, resulting in greater thickness.), as in Claim 10.
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Ramirez in view of Slatter et al. (US 2020/0224246 A1), hereinafter “Slatter”. Ramirez has been discussed above.
Regarding Claim 9, the prior art meets the limitations of Claim 1 as discussed above. Further, Ramirez does not specifically teach the flow cell discussed above wherein the reactive entity in each of the plurality of reactive regions is an enzyme tag, as in Claim 9.
However, Slatter teaches a respective flow cell wherein a reactive entity immobilized on a surface of the flow cell is a transposome complex that enables tagmentation (such as commensurately seen as an enzyme tag given Applicant’s specification para. [0117]), wherein tagmentation is a DNA preparation technique (performed prior to sequencing by synthesis) that combines two traditional DNA library preparation steps — fragmentation and adapter ligation — into a single enzymatic reaction ([0029]). As Ramirez relies on fragmentation ([0002-0003] and [0359]) and adapter ligation ([0066-0068]), one of ordinary skill in the art would find it obvious to combine the two steps into a singular tagmentation reaction via an enzyme tag in the plurality of reactive regions so as to reduce the number of reaction and purification steps, thereby improving the yield of primers and accuracy of sequencing given fewer strands would be lost across plural preparation steps rather than a single preparation step implemented directly into the flow cell.
Thus, one of ordinary skill in the art before the effective filing date of the claimed invention would have found it obvious to modify the flow cell of Ramirez wherein the reactive entity in each of the plurality of reactive regions is an enzyme tag, such as suggested by Slatter, so as to improve the yield of primers and accuracy of sequencing, and would have a reasonable expectation of success in Ramirez given that Ramirez is drawn to a commensurately formed flow cell with attachment points to which the enzyme tag may be attached.
Claims 11-12 are rejected under 35 U.S.C. 103 as being unpatentable over Ramirez in view of Hansen et al. (US 2020/0330984 A1), hereinafter “Hansen”. Ramirez has been discussed above.
Regarding Claim 11, the prior art meets the limitations of Claim 1 as discussed above. Further, Ramirez teaches the flow cell discussed above wherein:
the substrate 12 includes a plurality of depressions 14 (See Figs. 3 and 5J showing the depressions 14 in the substrate 12.); each of the plurality of reactive regions is positioned within a respective one of the plurality of depressions (See Figs. 3 and 5J showing the depressions 14 holding the reactive regions having the primers 22. See also [0191]: “Generally, the patterned substrate 12 includes depressions 14 separated by interstitial regions 16, and surface chemistry 20, 22 positioned in the depressions 14.”), as in Claim 11.
Further as in Claim 11, Ramirez does not specifically teach the flow cell discussed above wherein each of the independently removable coatings is a photo-cleavable protective layer, as in Claim 11.
However, Hansen teaches a respective flow cell ([0053]) having a well arrangement containing biological samples 14, wherein said biological samples 14 are preserved and protected by a photo-cleavable protective layer 16’ (Fig. 1C) so as to preserve and seal said samples in the wells for future study ([0008, 0054]), and wherein the photo-cleavability of the layer 16’ enables individual wells of interest to be opened using patterned UV light for selective release and retrieval ([0007]).
Thus, one of ordinary skill in the art before the effective filing date of the claimed invention would have found it obvious to modify the flow cell of Ramirez wherein each of the independently removable coatings is a photo-cleavable protective layer, such as suggested by Hansen, so as to provide a selectively-removeable protective layer such that the individual depressions of Ramirez may be deprotected selectively, thereby enabling multiple-use of the flow cell via later deprotection of unused wells and/or optimization of the number of available reactive zones needed for the assay at hand or number of expected fragments, and would have a reasonable expectation of success in Ramirez because the skilled artisan need only exchange the protective layer solution for forming the protective layer in Ramirez for one forming a photo-cleavable protective layer.
Regarding Claim 12, the prior art meets the limitations of Claim 11 as discussed above. Further, as discussed above regarding Claim 11, the skilled artisan would find it obvious to provide the photo-cleavable protective layer of Hansen as the protective layer in Ramirez so as to enable selective deprotection of the respective photo-cleavable layers. Therein, the photo-cleavable protective layer of Hansen is provided as a hydrophilic PEG polymer cross-linked with a photo-cleavable cross-linker (See Figs. 2B-2C showing cleavage of the cross-linker upon exposure to UV light ([0013-0014]). – See also [0061]. – Further note that PEG is a hydrophilic polymer given by the charged nitro groups.). Therein, one skilled in the art would find it obvious to use the specified photo-cleavable β-thioether cross-linker polymer protective layer as in paras. [0013-0014] and [0061] so as to provide a suitable photo-cleavable layer-forming species for achieving the desired selective deprotection of respective wells.
Thus, one of ordinary skill in the art before the effective filing date of the claimed invention would have found it obvious to provide the flow cell of Ramirez/Hansen as in Claim 11 wherein the photo-cleavable protective layer is a hydrophilic polymer cross-linked with a photo-cleavable cross-linker, such as suggested by Hansen, so as to provide a sufficient photo-cleavable structure/substance for achieving the sought selective well deprotection of Hansen in the flow cell of Ramirez, and would have a reasonable expectation of success in Ramirez merely being a particular polymer replacing that already present in Ramirez.
Claim 13 is rejected under 35 U.S.C. 103 as being unpatentable over Ramirez in view of Hansen, as applied to Claims 11-12 above, and in further view of Meagley (US 2008/0160446 A1), hereinafter “Meagley”.
Regarding Claim 13, the prior art meets the limitations of Claim 11 as discussed above. Further, Ramirez/Hansen does not specifically teach the flow cell discussed above wherein the photo-cleavable protective layer is a hydrophilic polymer capped with a photo-cleavable hydrophobic group or an acid-labile group, as in Claim 13.
However, Meagley teaches photoresist compositions comprising a hydrophilic polymer (Meagley discusses amino-acid polymers, which are hydrophilic.) having hydrophobic protecting groups attached thereto ([0019]), so as to prevent the polymer from dissolving in water ([0017]: “This protection may help to change, often reduce, the dissolution of the amino acid polymer in a developer. Thus, in one aspect, the protecting group may be considered a “dissolution inhibitor”.”) until a light beam is applied to the polymer, cleaving off the hydrophobic protecting groups and thereby solubilizing the otherwise water-soluble polymer ([0018]: “The amino acid polymer may be included in a photoresist composition with a photo-acid generator (PAG) or other species capable of generating an acid upon exposure to radiation. The radiation applied to the photoresist may cause the decomposition of the PAG, which may cause the generation of a small amount of acid catalyst throughout the exposed resist. The acid, once generated, may cause a cascade of chemical reactions either instantly or in a post-exposure bake that increase the solubility of the resist such that the exposed portions of the resist may be removed by a developer.”). Therein, the skilled artisan would find it obvious to utilize this arrangement as a suitable polymer structure for achieving the controlled solubility sought by Ramirez/Hansen for controlled deprotection.
Thus, one of ordinary skill in the art before the effective filing date of the claimed invention would have found it obvious to modify the flow cell of Ramirez/Hansen wherein the photo-cleavable protective layer is a hydrophilic polymer capped with a photo-cleavable hydrophobic group, such as suggested by Meagley, so as to provide a sufficient photo-cleavable structure/substance for achieving the sought selective well deprotection of Ramirez/Hansen, and would have a reasonable expectation of success in Ramirez merely being a particular polymer replacing that already present in Ramirez.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BENJAMIN KASS whose telephone number is (703)756-5501. The examiner can normally be reached Monday - Friday from 9:00 A.M. to 5:00 P.M. EST. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Charles Capozzi, can be reached at telephone number (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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/B.J.K./Examiner, Art Unit 1798
/P. Kathryn Wright/Primary Examiner, Art Unit 1798
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