Office Action 1: Non-Final Rejection (2024-10-16)
Rejection types: 102 - Lack of Novelty, 103 - Obviousness, 112 - Written Description/Enablement, Double Patenting

CLAIMS:
CLAIMS
1\. An array of polynucleotide molecules on a surface, wherein said surface comprises nucleotide binding regions separated by non-nucleotide binding regions; wherein the nucleotide binding regions comprise nucleotide capture chemistry and the non-nucleotide binding regions do not have the nucleotide capture chemistry; wherein more than 50% of the nucleotide binding regions in the array are occupied with one of the polynucleotide molecules; and wherein said surface is not a bead.
2\. The array of claim 1 wherein said surface is a patterned surface.
3\. The array of claim 1, wherein said nucleotide binding regions are discrete spaced apart regions.
4\. The array of claim 3, wherein said non-nucleotide binding regions are inter-regional areas that separate said discrete spaced apart regions.
5\. The array of claim 3, wherein said nucleotide binding regions are arranged in a grid pattern.
6\. The array of claim 1, wherein said polynucleotide molecules are linear or branched.
7\. The array of claim 1, wherein more than 105 different polynucleotide molecules are present on the array.
8\. The array of claim 1, wherein sequences of said polynucleotide molecules attached on the nucleotide binding regions are not known.
9\. The array of claim 8, wherein said polynucleotide molecules are generated from genomic DNA, cDNA, or RNA.
10\. The array of claim 1, wherein said nucleotide capture chemistry is a plurality of oligonucleotides in each nucleotide binding region that binds said polynucleotide molecules.
11\. The array of claim 10, wherein at least part of the sequences of oligonucleotides in the nucleotide binding regions is identical.
12\. The array of claim 11, wherein said oligonucleotides capture the polynucleotide molecules through identical parts of the oligonucleotide sequences.
13\. The array of claim 10, wherein said oligonucleotides are 20 to 100 bases in length.
14\. The array of claim 10, wherein said oligonucleotides are produced by nano-printing techniques, or by creating active sites for oligonucleotide attachment using photochemistry.

OFFICE ACTION:
DETAILED ACTION
Notice of Pre-AIA  or AIA  Status
1.	The present application is being examined under the pre-AIA  first to invent provisions.
Claim Rejections - 35 USC § 112
2.	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.
3.	Claims 9, 11, and 12 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.
A.	Claim 9 is a product claim that recites a method step, “said polynucleotides are generated from…” Having a method limitation within a product claim raises an issue as to when the claim is infringed, therefore the claim is indefinite, see MPEP 2173.05(p).
B.	Claim 11 is indefinite because it recites that “at least part of the sequences in the nucleotide binding regions is identical” and it is not clear if this means that sequences within a single binding region are identical to each other, or if sequences in different binding regions must be identical.  That is, it is not clear what the identity must be with.  This is further complicated by the recitation that it is only “at least part” of the sequences because it is unclear if this means that an individual sequence must have identity within itself (repeats) or if “part” of an individual sequence must be identical to “part” of another individual sequence either within the same binding region or with a molecule or molecules in a different binding region.  Since “part” can be one nucleotide of a sequence it is not really clear what limitation is intended.
C. Claim 12 is rejected because it depends from rejected claim 11.
Claim Rejections - 35 USC § 102
4.	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.
5.	The following is a quotation of the appropriate paragraphs of pre-AIA  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 –
(e) the invention was described in (1) an application for patent, published under section 122(b), by another filed in the United States before the invention by the applicant for patent or (2) a patent granted on an application for patent by another filed in the United States before the invention by the applicant for patent, except that an international application filed under the treaty defined in section 351(a) shall have the effects for purposes of this subsection of an application filed in the United States only if the international application designated the United States and was published under Article 21(2) of such treaty in the English language.
6.	Claims 1-7, 10-14 are rejected under pre-AIA  35 U.S.C. 102(e) as being anticipated by Kris et al (US Patent Application No. US 20050239097 A1, filed 2004-10-07, hereafter referred to as Kris).
With regard to claim 1, Kris teaches an array of anchor molecules ([0002]) arranged on a surface ([0003]), wherein anchor molecules are oligonucleotides ([0007]). Kris teaches that these surfaces comprise spatially discrete regions, each region comprises anchor molecules (i.e., oligonucleotide capture chemistry), and that these regions are separated from one another by blank spaces on the surface in which there are no anchors ([0021]).
Kris teaches that each anchor molecule is associated with a bifunctional linker molecule ([0002]) and that these linker molecules are oligonucleotides (i.e., polynucleotides [0017]). Each anchor molecule being associated with a linker teaches that more than 50% of the nucleotide binding regions are occupied with one of the polynucleotide molecules.
Kris additionally teaches a preferred embodiment wherein the surface is the plastic surface of a multiwell plate ([0020]).
With regard to claim 2, Kris teaches that the orientation of the test regions are parallel arrays within a rectangular surface (i.e., a grid pattern [0021]).
With regard to claim 3, Kris teaches that the regions of the array are spatially discrete and separated (i.e., spaced apart [0021]).
With regard to claim 4, the array of claim 3 is discussed above. Kris teaches regions on the surface are separated by blank spaces in which there are no anchor molecules (i.e., non-nucleotide binding [0021]).
With regard to claim 5, the array of claim 3 is discussed above. Kris teaches that the orientation of test regions are parallel arrays within a rectangular surface (i.e., a grid pattern [0021]).
With regard to claim 6, the array of claim 1 is discussed above. Kris teaches linker oligonucleotides (i.e., polynucleotides) that are linear (Figure 1 and [0017]).
With regard to claim 7, Kris teaches that a surface comprises 1536 shallow wells ([0017]), and that each well comprises additional smaller wells (e.g., 36 additional wells [0025]), each comprising a group of 4 anchor oligonucleotides (i.e., polynucleotides [0027]), and each anchor molecule being bound to a linker molecule (i.e., another polynucleotide [0017]). This teaching provides an array of 1536 x 36 x (4 x 2), or 442,368, polynucleotides on the surface.
With regard to claim 10, Kris teaches that anchor molecules (i.e., nucleotide capture chemistry) are oligonucleotides ([0007]). Additionally, Kris teaches that each test region comprises a group (i.e., a plurality) of anchor molecules ([0027]).
With regard to claim 11, the array of claim 10 is discussed above. Kris teaches that the anchor oligonucleotides are “generic” (i.e., identical [0002]).
With regard to claim 12, the array of claim 11 is discussed above. Kris teaches that the generic anchor oligonucleotides interact with the linker polynucleotides through a corresponding “anchor-specific” portion of the linker ([0034]).
With regard to claim 13, the array of claim 10 is discussed above. Kris teaches in example 1 that all anchor oligonucleotides are 25 nucleotides (i.e., bases) in length ([0171], Anchors #1-7).
With regard to claim 14, the array of claim 10 is discussed above. Kris teaches that anchor oligonucleotides are distributed onto a surface in a volume of 10.4 nanoliters using a nanojet dispenser (i.e., nano-printing [0046]).
Claim Rejections - 35 USC § 103
7.	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.
8.	The following is a quotation of pre-AIA  35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negated by the manner in which the invention was made.
9.	This application currently names joint inventors. In considering patentability of the claims under pre-AIA  35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary.  Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA  35 U.S.C. 103(c) and potential pre-AIA  35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA  35 U.S.C. 103(a).
10.	Claims 8 and 9 are rejected under pre-AIA  35 U.S.C. 103(a) as being unpatentable over Kris as applied to claim 1 above, and further in view of Lapidus et al (US Patent Application No. US 20060024711 A1, with a priority date to 2004-07-02.
With regard to claim 8, the array of claim 1 is discussed above and incorporated here fully. Kris teaches that anchor molecules (i.e., nucleotide capture chemistry) are associated with linker molecules (i.e., polynucleotides [0002]).
Kris does not teach that the sequences of these polynucleotides are not known.
However, Lapidus teaches the sequencing of a nucleic acid template wherein regions of the template have sequences that are not known ([0052]). Additionally, Lapidus teaches that these templates are hybridized to primers arrayed on a substrate (Figure 2B). With regard to claim 9, Lapidus teaches that the circular nucleic acid template (i.e., a polynucleotide) is genomic DNA, cDNA, or RNA ([0071]).
It would have been obvious to one of ordinary skill in the art to substitute the known linker polynucleotide disclosed by Kris with the unknown circular template disclosed by Lapidus to arrive at the instantly claimed invention with a reasonable expectation of success. Additionally, it would have been obvious to an ordinary artisan that the generic anchor oligonucleotide taught by Kris could act as a primer to amplify the circular template taught by Lapidus allowing the array disclosed by Kris to be used for the concatemer sequencing reactions disclosed by Lapidus. It would have been obvious to the ordinary artisan that this substitution could be made with predictable results, because the known techniques of the cited references predictably result in techniques for the preparation of nucleic acid arrays and performing nucleic acid reactions on an array surface.
Double Patenting
10.	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.
11.	Claims 1-5, and 7-1 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1- of U.S. Patent No. US 10351909 B2. Although the claims at issue are not identical, they are not patentably distinct from each other because while the instant claim set is drawn to an array of polynucleotides, claim 1 of the patent is drawn to a method providing a similar array of polynucleotides.
With regard to claim 1 of the instant application, claim 1 of the patent teaches:
A.	An array of DNA (i.e., polynucleotides) on a surface;
B.	said surface comprises nucleotide binding regions separated by non-nucleotide binding regions;
C.	nucleotide binding regions comprise nucleotide capture chemistry and the non-nucleotide binding regions do not have the nucleotide capture chemistry;
D.	more than 50% of the nucleotide binding regions in the array are occupied with one of the polynucleotide molecules;
E.	said surface is not a bead.
With regard to claim 2 of the instant application, claim 1 of the patent discloses that the surface is patterned (“a pattern of DNA binding regions…”).
With regard to claim 3 of the instant application, claim 1 of the patent discloses that the DNA (i.e., nucleotide) binding regions are separated (i.e., discrete).
With regard to claim 4 of the instant application, claim 1 of the patent discloses that the discrete spaced apart regions are separated by non-DNA binding surface.
With regard to claim 5 of the instant application, claim 6 of the patent discloses that the DNA binding regions are arranged in a grid pattern.
With regard to claim 7 of the instant application, claim 1 of the patent discloses that there are more than 105 different DNAs are bound on the array.
With regard to claim 8 of the instant application, claim 1 of the patent discloses that the sequence of the DNA at each binding region is not known.
With regard to claim 9 of the instant application, claim 1 of the patent discloses that the DNA bound to the array is genomic DNA.
With regard to claim 10 of the instant application, claim 1 of the patent discloses that the DNA binding regions comprise oligonucleotides for binding the DNAs (i.e., nucleotide capture chemistry).
With regard to claim 11 of the instant application, claim 1 of the patent discloses that all of the DNA binding regions comprise the same oligonucleotides.
With regard to claim 12 of the instant application, claim 1 of the patent discloses that all of the DNA binding oligonucleotides are the same (i.e., identical), therefore they capture the polynucleotide molecules through identical parts of the oligonucleotide sequences.
Therefore the inventions as defined by the claim sets are anticipated by the claims of the issued patent.
Claims 6, 13 and 14 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. US 10351909 B2 in view of Kris et al(US Patent Application No. US 20050239097, filed 2004-10-7, hereafter referred to as Kris).
The limitations of claims 6, 13 and 14 are not disclosed in the patent.
However, Kris teaches the limitations of claims 6, 13 and 14 as discussed fully above and incorporated here.
It would have been obvious to modify the claims of the patent to include these limitations. An ordinary artisan would have been motivated to make these modifications because Kris’s teachings provide additional advantages in describing the characteristics of polynucleotides on an array surface, as well as describing techniques for patterning polynucleotides on an array surface. In addition, it would have been obvious to one of ordinary skill in the art that the known techniques of the cited reference could have been combined with the claims of the patent with predictable results, because both techniques relate to the use of oligonucleotides arrayed on a substrate.
12.	Claims 1-5  rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1- of U.S. Patent No. US 9944984 B2. Although the claims at issue are not identical, they are not patentably distinct from each other because both the claim sets are drawn to arrays of DNA (i.e., polynucleotides) on a surface.
With regard to claim 1 of the instant application, claim 10 of the patent teaches:
A.	An array of DNA (i.e., polynucleotides) on a surface;
B.	said surface comprises nucleotide binding regions separated by non-nucleotide binding regions;
C.	nucleotide binding regions comprise nucleotide capture chemistry and the non-nucleotide binding regions do not have the nucleotide capture chemistry;
D.	more than 50% of the nucleotide binding regions in the array are occupied with one of the polynucleotide molecules;
E.	said surface is not a bead.
With regard to claim 2 of the instant application, claim 8 of the patent discloses that the surface is patterned (“a pattern of DNA binding regions…”).
With regard to claim 3 of the instant application, claim 10 of the patent discloses that the DNA (i.e., nucleotide) binding regions are separated (i.e., discrete).
With regard to claim 4 of the instant application, claim 10 of the patent discloses that the discrete spaced apart regions are separated by non-DNA binding surface.
With regard to claim 5 of the instant application, claim 8 of the patent discloses that the DNA binding regions are arranged in a grid pattern.
With regard to claim 7 of the instant application, claim 10 of the patent discloses that there are more than 105 different DNAs are bound on the array.
With regard to claim 8 of the instant application, claim 10 of the patent discloses that the sequence of the DNA at each binding region is not known.
With regard to claim 9 of the instant application, claim 10 of the patent discloses that the DNA bound to the array is genomic DNA.
With regard to claim 10 of the instant application, claim 10 of the patent discloses that the DNA binding regions comprise oligonucleotides for binding the DNAs (i.e., nucleotide capture chemistry).
With regard to claim 11 of the instant application, claim 10 of the patent discloses that all of the DNA binding regions comprise the same oligonucleotides.
With regard to claim 12 of the instant application, claim 10 of the patent discloses that all of the DNA binding oligonucleotides are the same (i.e., identical), therefore they capture the polynucleotide molecules through identical parts of the oligonucleotide sequences.
Therefore the inventions as defined by the claim sets are anticipated by the claims of the issued patent.
Claims 6, 13 and 14 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. US 10351909 B2 in view of Kris et al (US Patent Application No. US 20050239097, filed 2004-10-7, hereafter referred to as Kris).
The limitations of claims 6, 13 and 14 are not disclosed in the patent.
However, Kris teaches the limitations of claims 6, 13 and 14 as discussed fully above and incorporated here.
It would have been obvious to modify the claims of the patent to include these limitations. An ordinary artisan would have been motivated to make these modifications because Kris’s teachings provide additional advantages in describing the characteristics of polynucleotides on an array surface, as well as describing techniques for patterning polynucleotides on an array surface. In addition, it would have been obvious to one of ordinary skill in the art that the known techniques of the cited reference could have been combined with the claims of the patent with predictable results, because both techniques relate to the use of oligonucleotides arrayed on a substrate.
13.	Claims 1- rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-36 of U.S. Patent No. US  in view of Kris (US Patent Application No. US 20050239097, filed 2004-10-7).
With regard to claim 1 of the instant application, claims 2 and 5 of the patent and Kris teach:
A.	An array of DNA (i.e., polynucleotides) on a surface;
B.	said surface comprises nucleotide binding regions separated by non-nucleotide binding regions;
C.	nucleotide binding regions comprise nucleotide capture chemistry and the non-nucleotide binding regions do not have the nucleotide capture chemistry;
D.	more than 50% of the nucleotide binding regions in the array are occupied with one of the polynucleotide molecules;
E.	said surface is not a bead.
The patent does not teach all of the limitations instant claim 1 in a single claim.  However, it would have been obvious to one having ordinary skill in the art to have modified the patent claims to combine these disclosed elements because they are all disclosed in the patent claims as preferred embodiments of the invention.
With regard to claim 2 of the instant application, claim 1 of the patent discloses that the surface is patterned (“a pattern of DNA binding regions…”).
With regard to claim 3 of the instant application, claim 1 of the patent discloses that the DNA (i.e., nucleotide) binding regions are separated (i.e., discrete).
With regard to claim 4 of the instant application, claim 1 of the patent discloses that the discrete spaced apart regions are separated by non-DNA binding surface.
With regard to claim 10 of the instant application, claim 7 of the patent discloses that the DNA binding regions comprise oligonucleotides for binding the DNAs (i.e., nucleotide capture chemistry).
The patent does not teach the limitations of claims 5-7 and 11-14, however, Kris discloses these limitations as discussed fully above and incorporated here.
It would have been obvious to modify the claims of the patent to include these limitations. An ordinary artisan would have been motivated to make these modifications because Kris’s teachings provide additional advantages in describing the characteristics of polynucleotides on an array surface, as well as describing techniques for patterning polynucleotides on an array surface. In addition, it would have been obvious to one of ordinary skill in the art that the known techniques of the cited reference could have been combined with the claims of the patent with predictable results, because both techniques relate to the use of oligonucleotides arrayed on a substrate.
Claims 8 and 9 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-36 of U.S. Patent No. 9650673 in view of Lapidus et al (US Patent Application No. US 20060024711 A1, with a priority date to 2004-07-02, hereafter referred to as Lapidus).
The patent does not teach the limitations for claims 8 and 9. However, Lapidus discloses these limitations as discussed fully above and incorporated here.
It would have been obvious to one of ordinary skill in the art to substitute the known linker polynucleotide disclosed by Kris with the unknown circular template disclosed by Lapidus to arrive at the instantly claimed invention with a reasonable expectation of success. Additionally, it would have been obvious to an ordinary artisan that the generic anchor oligonucleotide taught by Kris could act as a primer to amplify the circular template taught by Lapidus allowing the array disclosed by Kris to be used for the concatemer sequencing reactions disclosed by Lapidus. It would have been obvious to the ordinary artisan that this substitution could be made with predictable results, because the known techniques of the cited references predictably result in techniques for the preparation of nucleic acid arrays and performing nucleic acid reactions on an array surface.
14.	Claims 1 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 of U.S. Patent No. US 8445196 B2 in view of Kris (US Patent Application No. US.
With regard to claim 1 of the instant application, the claims of the patent in combination with Kris teach:
A.	An array of DNA (i.e., polynucleotides) on a surface; Claim 20
B.	said surface comprises nucleotide binding regions separated by non-nucleotide binding regions; Claim 20
C.	nucleotide binding regions comprise nucleotide capture chemistry and the non-nucleotide binding regions do not have the nucleotide capture chemistry; Claim 20
D.	more than 50% of the nucleotide binding regions in the array are occupied with one of the polynucleotide molecules; Claim 20
E.	said surface is not a bead. This limitation is disclosed by Kris as fully discussed above and incorporated here.
With regard to claim 2 of the instant application, claim 21 of the patent discloses that the spaced apart regions are arranged in a rectilinear pattern.
With regard to claim 3 of the instant application, claim 15 of the patent discloses that the DNA (i.e., nucleotide) binding regions are discrete spaced apart regions.
With regard to claim 4 of the instant application, claim 20 of the patent discloses that the discrete spaced apart regions are separated by non-DNA binding surface.
With regard to claim 8 of the instant application, claim 15 of the patent discloses that the concatemers comprise polynucleotides of unknown sequence.
With regard to claim 9 of the instant application, claim 17 of the patent discloses that the target polynucleotide is an unknown sequence.
The patent does not teach limitation E of claim 1 or the limitations of claims 5-7 and 10-14 of the instant application, however, Kris discloses these limitations as discussed fully above and incorporated here.
It would have been obvious to modify the claims of the patent to include these limitations. An ordinary artisan would have been motivated to make these modifications because Kris’s teachings provide additional advantages in describing the characteristics of polynucleotides on an array surface, as well as describing techniques for patterning polynucleotides on an array surface. In addition, it would have been obvious to one of ordinary skill in the art that the known techniques of the cited reference could have been combined with the claims of the patent with predictable results, because both techniques relate to the use of oligonucleotides arrayed on a substrate.
15.	Claims 1 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. US 8133719 B2 in view of Kris (US Patent Application No. US.
With regard to claim 1 of the instant application, the claims of the patent in combination with Kris teach:
A.	An array of DNA (i.e., polynucleotides) on a surface; Claim 13
B.	said surface comprises nucleotide binding regions separated by non-nucleotide binding regions; Claim 13
C.	nucleotide binding regions comprise nucleotide capture chemistry and the non-nucleotide binding regions do not have the nucleotide capture chemistry; Claim 13
D.	more than 50% of the nucleotide binding regions in the array are occupied with one of the polynucleotide molecules; Claim 13
E.	said surface is not a bead. This limitation is disclosed by Kris as fully discussed above and incorporated here.
With regard to claim 3 of the instant application, claim 13 of the patent discloses that the DNA (i.e., nucleotide) binding regions are discrete spaced apart regions.
With regard to claim 4 of the instant application, claim 13 of the patent discloses that the discrete spaced apart regions are separated by non-DNA binding surface.
With regard to claim 8 of the instant application, claim 13 of the patent discloses that the concatemers comprise polynucleotides of unknown sequence.
With regard to claim 9 of the instant application, claim 13 of the patent discloses that the target polynucleotide is an unknown sequence.
The patent does not teach limitation E of claim 1 or limitations 2, 5-7 and 10-14 of the instant application, however, Kris discloses these limitations as discussed fully above and incorporated here.
It would have been obvious to modify the claims of the patent to include these limitations. An ordinary artisan would have been motivated to make these modifications because Kris’s teachings provide additional advantages in describing the characteristics of polynucleotides on an array surface, as well as describing techniques for patterning polynucleotides on an array surface. In addition, it would have been obvious to one of ordinary skill in the art that the known techniques of the cited reference could have been combined with the claims of the patent with predictable results, because both techniques relate to the use of oligonucleotides arrayed on a substrate.
Conclusion
16.	No claim is allowed.
17.

APPLICANT REBUTTAL: REMARKS
This is a response to the first action on the merits of the claimed invention, dated October 16,
2024. This amendment and the terminal disclaimer being filed in this application place the application in condition for allowance. Applicants request that the application be reconsidered in view of the amendments presented above and the remarks that follow.
Claim amendments
Claims 1-14 were previously pending in this application and have been rejected. Some of the
claims are amended above. Claim 2 is cancelled; claims 15-20 are new. Accordingly, claims 1 and 3-20 are now pending and under examination.
The amendments to the claims do not add new matter into the disclosure. Polynucleotides
arranged in a pattern (previously referred to in claim 2) is now a feature of claim 1. Claims 10 to 12 as amended are supported in   [0030] of the application as published (US 2024/0301486 A1). Claim 15 is supported by claim 8 as originally filed. Claim 16 is supported, for example, by Fig. 1H of the application as filed. Claim 17 is supported by original claims 1 and 8. Claims 18 to 20 mirror claims 10 to 12 as amended.
The claim amendments are made without prejudice. Applicant reserves the right to reintroduce claims to the canceled subject matter or anything else disclosed in the specification, drawings, and claims as originally filed in this or another application.
Substitute specification
In related application 18/592,843, at the examiner's request, a substitute specification was filed, in which trade names and marks used in commerce were acknowledged.
The substitute specification accompanying this amendment is offered for the same purpose. Marks are indicated with the symbol ® or TM at their first occurrence in each section. Generic or functional equivalents are added if not already present. Otherwise there are no changes. No new matter is introduced into the application.
Rejections under 35 USC
&
Claims 9, 11, and 12 have been rejected under § 112   2 for reasons of claim wording. The
amendments presented above address the matters raised in the office action. Applicant requests that these rejections be withdrawn.
Rej
ection under 35 USC
?
Claims 1-7 and 10-14 have been rejected under § 102(e) as being anticipated by pre-grant publication US 2005/0239097 Al ("Kris"). According to the office action (page 4), Kris teaches:
(a) an array of oligonucleotide anchor molecules arrange on a surface in spatially discreate
regions, separated by blank spaces on the surface in which there are no anchors; and
(b) more than 50% of the anchor molecule is associated with a bifunctional oligonucleotide
linker molecule.
On this basis, the office action concludes that all the features of claim 1 of this application are taught by Kris. The office action identifies additional features in Kris that it says anticipate claims 2-7 and 11-14.
Applicant respectfully disagrees. In order to demonstrate anticipation, the proponent must show "that the four corners of a single, prior art document describe every element of the claimed invention." Advanced Display Sys., Inc. v. Kent State Univ., 212 F.3d 1272, 1282 (Fed. Cir. 2000). Moreover, the reference must also disclose those elements "arranged as in the claim." Connell v. Sears, Roebuck & Co., 722 F.2d 1542, 1548 (Fed. Cir. 1983).
Paragraph [0017] of Kris explains the drawings this way:
FIG. 2, contains 15 identical test regions; in an especially preferred embodiment of the invention,
each of these test regions is a well in a microtiter plate. Each of the test regions contains six
different anchors, here indicated as numbers 1-6. FIG. 1 schematically illustrates one of those anchors, [to which] is attached a linker molecule, linker 1, which comprises two portions. The
first portion, which is specific for the anchor, is in this illustration an oligonucleotide which can
hybridize specifically to the anchor. ... Although not illustrated in this figure, each of the
remaining five anchors can hybridize to its own linker via the anchor-specific portion.
[0027] of Kris says this:
The number of anchors in a test region can be at least two, preferably between about 8 and about
900 (more or less being included), more preferably between about 8 and about 300, and most preferably between about 30 and about 100 (e.g., about 64). In some preferred embodiments, there are about 16, 36, 45 or 100 anchors/test region for a surface with 96 test, regions (e.g.,
wells), or about 9, 16 or 25 anchors/test region for a surface with 384 test regions (e.g., wells)
Thus, each test region comprises a plurality of the same anchor - and the number of identical anchors in each test region is preferably about 64.
The office action equates Kris's "test regions" with the "binding regions" referred to in claim 1 of this application. In both cases, the regions are separated by inert parts of the surface that do not bind polynucleotides. However, according to   [0027] in Kris, their test regions are occupied not by one anchor, but by 64 anchors. Kris does not teach how to control the attachment of the anchors in each region so that the number of anchors bound is an exact number. Kris certainly does not teach a technology that would enable the user to reliably make separated test regions that bear only one or two anchors per region.
In Kris's preferred embodiment, the 64 anchors in each test regions would bind 64 linkers, which in turn would bind up to 64 target mRNAl molecules, followed by 64 detection reagent molecules. The number of mRNA1 molecules per test region would increase in proportion to their concentration in the loading solution, up until the 64 anchors in each region are saturated. Concentration dependent increase in the number of target mRNAl molecules bound is demonstrated in the data shown in Kris's Fig. 13.
Because the reaction is concentration dependent, the number of mRNAl molecules that would bind in each one of the test regions would accord with the Poisson distribution:
Probability mass function
ke-A
The Poisson distribution dictates that even at low concentrations, the largest proportion of Kris's test regions that will have one and only one mRNA1 polynucleotide molecule attached thereto can be no more than about 37%.
In contrast, claim 1 of this application states that more than 50% of the nucleotide binding
regions in the array are occupied with one of the polynucleotide molecules. The technology in this patent disclosure makes this possible because each binding region becomes saturated when the first polynucleotide is captured - whereupon no others can bind. This is clearly different anything that is taught and enabled in Kris's description.
Claim 2 has been cancelled. Claims 3-7, claims 10-14, and new claims 15-16 depend from and incorporate the features of claim 1, and are patentable for the same reasons. Applicant requests that this rejection be withdrawn.
Rejection
under 35 USC
(e) as being obvious over Kris in combination withpre-grant publication US 2006/0024711 Al ("Lapudis"). The office action states that although Kris does not teach that the sequence of the polynucleotide molecules is not known, it would have been obvious to substitute the known linker polynucleotide of Kris with the unknown circular template of Lapudis, thereby achieving the invention referred to in the claims presented here.
Applicant respectfully disagrees. The technologies of Kris and Lapudis are incompatible. In the technology of Kris depicted in Fig. 1 (reproduced above), the linker molecule serves the purpose of capturing a target mRNA1, which is then measured using the "Detection 1" reagent. Substituting the unknown circular template of Lapudis for Kris's linker molecule would render Kris inoperable - the unknown circular template it would not have the particular nucleotide sequence needed in Kris to bind to the target mRNA1 (and hence to the detection reagent). This obviates the rejection, since a proposed modification in a § 103 rejection cannot render the prior art unsatisfactory for its intended purpose. MPEP § 2143.01(V).
Furthermore, even if Kris and Lapudis were to be combined in the manner suggested in the office action, the combination would not suggest the invention claimed here. As explained above, there are a plurality (preferably 64) of anchor molecules in each of Kris's test regions. Substituting the circular template of Lapudis for the linker would change 64 linker molecules in each test region to 64 circular templates. This still doesn't meet the requirement of the claims that more than 50% of the nucleotide binding regions in the array are occupied with only one of the polynucleotide molecules.
Applicant requests that this rejection be withdrawn.
New claim 17 is an independent claim that combines features of claim 1 with features of claim 8, and is patentable for the same reasons. New claims 18 to 20 are patentable over the prior art of record because they depend from claim 17.
Double patenting
Certain claims pending in this application have been rejected under the doctrine of nonstatutory double patenting over the following related issued U.S. patents - either alone, or in combination with Kris (supra) and/or Lapudis (supra):
US 10,351,909: DNA sequencing from high density DNA arrays using asynchronous reactions (Complete Genomics Inc.)
US 9,944,984:   High density DNA array
(Complete Genomics Inc.)
US 9,650,673:   Single molecule arrays for genetic and chemical analysis; (Complete Genomics Inc.)
US 8,445,196:   Single molecule arrays for genetic and chemical analysis (Complete Genomics Inc.)
US 8,133,719:   Methods for making single molecule arrays (Complete Genomics Inc.)
A terminal disclaimer was filed in this application and approved by the office in relation to the patents listed above on January 11, 2025. This does not imply that applicant agrees with the analysis in the office action. No further remarks are made in this respect because the terminal disclaimer is sufficient to overcome the rejections.
Applicant requests that these rejections be withdrawn.
Interview re
q
uest
Applicant requests that this patent applicant be allowed forthwith. In the event that the examiner identifies other matters to be addressed, applicant requests a telephone interview between the examiner and the undersigned.
No fee is due for filing and consideration of this response. Nevertheless, the Commissioner is hereby authorized to charge any additional fees that may be required for further examination of this application or credit any overpayment to Deposit Account No. 20-1430.
KILPATRICK TOWNSEND & STOCKTON LLP 1302 El Camino Real, Suite 175 Menlo Park, CA 94025 Phone: 650-324-6340

NEXT OFFICE ACTION: Notice of Pre-AIA  or AIA  Status
1.	The present application is being examined under the pre-AIA  first to invent provisions.
Status of the Claims
2.	This action is in response to papers filed 13 January 2025 in which claims 1, 5, and 8-12 were amended, claim 2 was cancelled, and claims 15-20 were added.
The rejections in the Office Action dated 10 October 2024 under USC § 112 2nd are withdrawn in view of the amendments.
The previous rejections for double patenting were overcome by the filing of appropriate terminal disclaimers.
EXAMINER’S AMENDMENT
3.	An examiner’s amendment to the record appears below. Should the changes and/or additions be unacceptable to applicant, an amendment may be filed as provided by 37 CFR 1.312. To ensure consideration of such an amendment, it MUST be submitted no later than the payment of the issue fee.
4.	Authorization for this examiner’s amendment was given in an interview with Michael Schiff on 04 February 2025.
5.	The application has been amended as follows:
In claim 1, lines 6-7, the words ---a single--- were inserted between the word “with” and the word “one” so the claim now reads “…regions in the array are occupied with a single one of the polynucleotide molecules…”
REASONS FOR ALLOWANCE
6.	The following is an examiner’s statement of reasons for allowance:
The instantly claimed invention is drawn to an array of polynucleotides on a surface; wherein said surface comprises nucleotide binding reagents arranged on the surface in a predetermined pattern, and wherein more than 50% of the nucleotide binding regions in the array are occupied with a single one of the polynucleotide molecules, and wherein the surface is not a bead. The prior art does not teach or reasonably suggest the instantly claimed array as defined by the claim. The closest prior art is Kris (US Patent Application No. US 20050239097 A1, filed 2004-10-07), who teaches an array comprising the polynucleotide molecules of the claim but does not teach that more than 50% of the binding regions are occupied with a single one of these polynucleotide molecules. The prior art does not provide a reason to modify the closet prior art to arrive at the claimed invention, and the Applicant’s argument that this feature is non-obvious is persuasive.
Any comments considered necessary by applicant must be submitted no later than the payment of the issue fee and, to avoid processing delays, should preferably accompany the issue fee.  Such submissions should be clearly labeled “Comments on Statement of Reasons for Allowance.”
Conclusion
7.	Claims 1 and 3-20 are allowed.
8.

CITED REFERENCE SUMMARIES: Ref US20050239097A1: Claims:
A method to detect one or more nucleic acids of interest, comprising subjecting a sample comprising said nucleic acid(s) to nuclease protection with one or more protection fragments, and detecting the hybridized duplex molecules, or the single strand protected nucleic acid(s), or the protection fragment(s).
The method of claim 1 , wherein the method is a high throughput method.
The method of claim 2 , wherein the nucleic acid(s) which is detected is a protection fragment(s).
The method of claim 3 , wherein at least two different protection fragments are detected.
The method of claim 3 , wherein at least 16 different protection fragments are detected.
The method of claim 2 , wherein the nucleic acid(s) which is detected is a hybridized duplex molecule.
The method of claim 2 , wherein the nucleic acid(s) which is detected is the protected nucleic acid.
The method of claim 2 , wherein said nucleic acid(s) of interest is measured.
The method of claim 8 , wherein the nucleic acid(s) which is measured is a protection fragment(s).
The method of claim 2 , wherein said protection fragment is modified chemically, and said chemical modification, with or without the nucleic acid portion of the protection fragment, is detected.
A combination useful for the detection of one or more target(s) in a sample, which comprises, before the addition of said sample, a) a surface, comprising multiple spatially discrete regions, at least two of which are substantially identical, each region comprising b) at least eight different oligonucleotide anchors, each in association with c) a bifunctional linker which has a first portion that is specific for the oligonucleotide anchor, and a second portion that comprises a probe which is specific for said target(s), wherein said surface has a) about 96 substantially identical regions, wherein each region comprises about 16, 36, 46 or 100 different oligonucleotide anchors, b) about 384 substantially identical regions, wherein each region comprises about 9, 16, or 25 different oligonucleotide anchors, or c) about 1536 substantially identical regions, wherein each region comprises about 4 or 9 different oligonucleotide anchors.
a) a surface, comprising multiple spatially discrete regions, at least two of which are substantially identical, each region comprising
b) at least eight different oligonucleotide anchors, each in association with
c) a bifunctional linker which has a first portion that is specific for the oligonucleotide anchor, and a second portion that comprises a probe which is specific for said target(s),
wherein said surface has
a) about 96 substantially identical regions, wherein each region comprises about 16, 36, 46 or 100 different oligonucleotide anchors,
b) about 384 substantially identical regions, wherein each region comprises about 9, 16, or 25 different oligonucleotide anchors, or
c) about 1536 substantially identical regions, wherein each region comprises about 4 or 9 different oligonucleotide anchors.
A method of detecting at least one target, comprising a) contacting a sample which may comprise said target(s) with the combination of claim 11 , under conditions effective for said target to bind to said combination, b) contacting said combination and any bound targets with a labeled detection probe, and c) detecting said detection probe.
a) contacting a sample which may comprise said target(s) with the combination of claim 11 , under conditions effective for said target to bind to said combination,
b) contacting said combination and any bound targets with a labeled detection probe, and
c) detecting said detection probe.
The method of claim 12 , wherein said labeled detection probe produces a chemiluminescent signal.
The method of claim 12 , wherein the target is measured.
A method of detecting at least one target, comprising a) contacting a sample which may comprise said target(s) with a bifunctional linker which has a first portion that is specific for an oligonucleotide anchor and a second portion that comprises a probe which is specific for said target(s), under conditions effective to obtain a first hybridization product between said target(s) and said linker, b) contacting said first hybridization product with a combination under conditions effective to obtain a second hybridization product between said first hybridization product and said combination, wherein said combination comprises, before the addition of said first hybridization product, 1) a surface comprising multiple spatially discrete regions, at least two of which are substantially identical, each region comprising 2) at least 8 different oligonucleotide anchors, c) contacting said first hybridization product or said second hybridization product with a labeled detector probe, and d) detecting said detection probe.
a) contacting a sample which may comprise said target(s) with a bifunctional linker which has a first portion that is specific for an oligonucleotide anchor and a second portion that comprises a probe which is specific for said target(s), under conditions effective to obtain a first hybridization product between said target(s) and said linker,
b) contacting said first hybridization product with a combination under conditions effective to obtain a second hybridization product between said first hybridization product and said combination, wherein said combination comprises, before the addition of said first hybridization product, 1) a surface comprising multiple spatially discrete regions, at least two of which are substantially identical, each region comprising 2) at least 8 different oligonucleotide anchors,
1) a surface comprising multiple spatially discrete regions, at least two of which are substantially identical, each region comprising
2) at least 8 different oligonucleotide anchors,
c) contacting said first hybridization product or said second hybridization product with a labeled detector probe, and
d) detecting said detection probe.
Ref US20060024711A1: Claims:
A method of determining a sequence of a nucleic acid, the method comprising the steps of: (a) conducting rolling circle amplification of a nucleic acid to produce an amplicon comprising about two to about one hundred linked complements of a nucleic acid; wherein said amplicon is anchored to a substrate, such that said amplicon is individually optically resolvable; and (b) determining a sequence of at least a portion of said nucleic acid.
(a) conducting rolling circle amplification of a nucleic acid to produce an amplicon comprising about two to about one hundred linked complements of a nucleic acid; wherein said amplicon is anchored to a substrate, such that said amplicon is individually optically resolvable; and
(b) determining a sequence of at least a portion of said nucleic acid.
The method of claim 1 , wherein said nucleic acid is genomic DNA, cDNA, or RNA.
The method of claim 1 , wherein said amplification step comprises circularizing said nucleic acid thereby forming a circular template; combining said circular template with a primer, a polymerizing agent, and nucleotides; and producing an amplicon comprising multiple linked complements of said circular template.
The method of claim 3 , wherein said primer binds to at least one of the 3′ end and the 5′ end of the nucleic acid.
The method of claim 1 , wherein said nucleic acid is single stranded.
The method of claim 1 , wherein said nucleic acid is double stranded, and wherein said amplification step further includes the step of denaturing said double stranded nucleic acid prior to combining with said primer.
The method of claim 1 , wherein said amplicon is anchored to said substrate after completion of said amplification step.
The method of claim 1 , wherein said amplicon is covalently bound to said substrate.
The method of claim 1 , wherein said amplicon is anchored to said substrate via a biotin-streptavidin complex.
The method of claim 1 , wherein said amplicon comprises a number of linked complements of the nucleic acid, said number determined by a concentration of nucleotides available for incorporation into said amplicon.
The method of claim 1 , wherein said substrate comprises an accumulation of negative charge.
The method of claim 1 , wherein said substrate comprises a plurality of loci for anchoring said amplicon.
The method of claim 1 , wherein said substrate is selected from the group consisting of glass, fused silica, epoxy, plastic, metal, gel matrix, and composites.
The method of claim 13 , wherein said substrate has a chemically modified surface comprising a polyelectrolyte multilayer.
The method of claim 1 , wherein said determining step comprises exposing said amplicon to a sequencing primer, a polymerizing agent, and at least one nucleotide; allowing incorporation of said nucleotide(s) into a synthesis strand; detecting incorporation of said nucleotide(s); and repeating said determining step at least once, thereby determining said sequence of said nucleic acid.
The method of claim 15 , wherein said determining step results in incorporation of about one or about two nucleotides into said synthesis strand.
The method of claim 15 , wherein said nucleotide is labeled with a fluorescent moiety.
The method of claim 1 , wherein said amplification step is performed with a primer that is anchored to said substrate such that upon completion of said amplification step, said amplicon is anchored to said substrate.
The method of claim 1 , wherein said amplification step is performed with a primer that is not anchored to said substrate such that upon completion of said amplification step, said amplicon is not attached to said substrate.
Ref US9650673: Claims:
1. An array comprising:
(a) a solid substrate comprising a surface, wherein said surface comprises a plurality of discrete regions defined on said surface,
wherein said discrete regions are arranged on the surface in a regular array and are separated by inter-regional areas;
(b) a population of concatemers randomly disposed on said plurality of discrete regions such that more than 95% of said plurality of discrete regions comprises a single concatemer attached thereto and said inter-regional areas are substantially free of concatemers, wherein said concatemers are generated from a circular template and comprise a plurality of monomeric units, wherein each monomeric unit comprises:
(i) a target sequence of a target polynucleotide, and
(ii) an adaptor,

and wherein said population of concatemers comprises a plurality of different target sequences.
2. The array of claim 1, wherein said discrete regions are positively charged so as to bind said concatemers.
3. The array of claim 2, wherein said concatemers have a diameter that is approximately equal to that of the discrete regions.
4. The array of claim 1, wherein said concatemers are non-covalently immobilized to said discrete regions.
5. The array of claim 1, wherein said inter-regional areas are hydrophobic.
6. The array of claim 1, wherein the regular array comprises a rectilinear pattern.
7. The array of claim 1, wherein said discrete regions comprise capture oligonucleotides.
8. The array of claim 1, wherein said discrete regions comprise an amino group.
9. The array of claim 1, wherein the target polynucleotide is human genomic DNA.
10. The array of claim 1, wherein said discrete regions are 100 to 300 nm in diameter.
11. The array of claim 1, wherein the concatemers randomly disposed on said discrete regions are attached to a positively charged surface that binds negatively charged DNA.
12. An array comprising:
(a) a solid substrate comprising a surface, wherein said surface comprises a plurality of discrete regions defined on said surface separated by inter-regional areas;
(b) a population of concatemers randomly disposed on the plurality of discrete regions such that more than 95% of said plurality of discrete regions comprise a single concatemer attached thereto and said inter-regional areas are substantially free of concatemers;
wherein said concatemers randomly disposed on said discrete regions are bound to a positively charged surface that binds negatively charged DNA;
wherein the discrete regions are arranged on the surface as a regular array;
wherein each said concatemer comprises a plurality of monomeric units, each unit comprising a target sequence of a target polynucleotide; and
wherein the population of concatemers comprises a plurality of different target sequences.
13. The array of claim 12 wherein said concatemers have a diameter that is approximately equal to that of the discrete regions.
14. The array of claim 12, wherein said inter-regional areas are hydrophobic.
15. The array of claim 12, wherein the target polynucleotide is human genomic DNA.
16. The array of claim 12, wherein said discrete regions are 100 to 300 nm in diameter.
17. The array of claim 12, wherein each concatemer contains a plurality of monomeric units, each comprising:
(i) a target sequence of a target polynucleotide, and
(ii) an adaptor.
18. The array of claim 1, wherein said concatemers have a diameter that is approximately equal to that of the discrete regions.
19. An array comprising:
(a) a solid substrate comprising a surface, wherein said surface comprises a plurality of discrete regions defined on said surface,
wherein said discrete regions are arranged on the surface in a regular array and are separated by inter-regional areas;
(b) a population of concatemers randomly disposed on said plurality of discrete regions such that at least a majority of said plurality of discrete regions comprises a single concatemer attached thereto and said inter-regional areas are substantially free of concatemers, wherein said concatemers are generated from a circular template and comprise a plurality of monomeric units, wherein each monomeric unit comprises:
(i) a target sequence of a target polynucleotide, and
(ii) an adaptor,

wherein said discrete regions
(i) have a diameter that is approximately equal to that of the concatemers, or
(ii) have a diameter of 100 to 300 nm

and wherein said population of concatemers comprises a plurality of different target sequences.
20. The array of claim 19, wherein said discrete regions are positively charged so as to bind said concatemers.
21. The array of claim 19, wherein said concatemers are non-covalently immobilized to said discrete regions.
22. The array of claim 19, wherein said inter-regional areas are hydrophobic.
23. The array of claim 19, wherein the regular array comprises a rectilinear pattern.
24. The array of claim 19, wherein more than 80% of said discrete regions have a single concatemer attached thereto.
25. The array of claim 19, wherein said discrete regions comprise capture oligonucleotides.
26. The array of claim 19, wherein said discrete regions comprise an amino group.
27. The array of claim 19, wherein the target polynucleotide is human genomic DNA.
28. The array of claim 19, wherein the concatemers randomly disposed on said discrete regions are attached to a positively charged surface that binds negatively charged DNA.
29. An array comprising:
(a) a solid substrate comprising a surface, wherein said surface comprises a plurality of discrete regions defined on said surface separated by inter-regional areas;
(b) a population of concatemers randomly disposed on the plurality of discrete regions such that more than 80% of said plurality of discrete regions comprise a single concatemer attached thereto and said inter-regional areas are substantially free of concatemers;
wherein said concatemers randomly disposed on said discrete regions are bound to a positively charged surface that binds negatively charged DNA;
wherein the discrete regions are arranged on the surface as a regular array;
wherein each said concatemer comprises a plurality of monomeric units, each unit comprising a target sequence of a target polynucleotide;
wherein said discrete regions
(i) have a diameter that is approximately equal to that of the concatemers, or
(ii) have a diameter of 100 to 300 nm, and

wherein the population of concatemers comprises a plurality of different target sequences.
30. The array of claim 29, wherein said inter-regional areas are hydrophobic.
31. The array of claim 29, wherein more than 95% of the discrete regions have a single concatemer attached thereto.
32. The array of claim 29, wherein the target polynucleotide is human genomic DNA.
33. The array of claim 29, wherein each concatemer contains a plurality of monomeric units, each comprising:
(i) a target sequence of a target polynucleotide, and
(ii) an adaptor.
34. The array of claim 12, wherein said discrete regions comprise an amino group.
35. The array of claim 29, wherein said discrete regions comprise an amino group.
36. The array of any one of claim 1, 12, 19 or 29 wherein the target polynucleotide comprised human genomic DNA.
Ref US10351909B2: Claims:
1. A method comprising:
a) initiating a first sequencing reaction on a first high density DNA array; and imaging said first high density DNA array using a detector, and
b) initiating a second sequencing reaction on a second high density DNA array; and imaging said second high density DNA array using the same detector,
wherein the first sequencing reaction is initiated before the second sequencing reaction is initiated such that the first sequencing reaction and the second sequencing reaction are non-synchronous,
wherein the first and second high density DNA arrays each independently comprise:
a patterned surface, said surface comprising a pattern of DNA binding regions separated by a non-DNA binding surface, and
more than 105 different DNAs comprising genomic sequences bound on the array at the DNA binding regions,
wherein the DNA binding regions comprise oligonucleotides for binding the DNAs within the DNA binding regions and all of the DNA binding regions of the array comprise the same oligonucleotides, and
wherein:
the density of the DNA binding regions on the array is more than 105 per mm2,
more than 50% of the DNA binding regions in the array have multiple copies of one single DNA of said more than 105 different DNAs,
the sequence of the single DNA at each DNA binding region is not known, and
the array is not a bead array.
2. A method comprising:
a) initiating a first sequencing reaction on a first high density DNA array; and imaging said first high density DNA array using a detector, and
b) initiating a second sequencing reaction on a second high density DNA array; and imaging said second high density DNA array using the same detector,
wherein the first sequencing reaction is initiated before the second sequencing reaction is initiated such that the first sequencing reaction and the second sequencing reaction are non-synchronous,
wherein the first and second high density DNA arrays each independently comprise:
a patterned surface, said surface comprising a pattern of DNA binding regions at a density of more than 105 DNA binding regions per mm2, separated by non-DNA binding regions of said surface,
wherein more than 50% of the DNA binding regions on said surface comprise multiple copies of a single genomic DNA sequence,
wherein the DNA binding regions on said surface comprise more than 105 different genomic DNA sequences,
wherein the genomic DNA sequences are randomly disposed on the array such that the genomic sequence at any given DNA binding region is not known prior to sequencing,
the more than 105 different genomic DNA sequences are linked to adaptor sequences,
the DNA binding regions comprise DNA capture oligonucleotides attached in the DNA binding regions and not attached to the non-DNA binding surface,
all of the DNA binding regions on the surface comprise the same attached capture oligonucleotides,
the capture oligonucleotides are complementary to the adaptors, and
wherein the array is not a bead array.
3. The method of claim 1, wherein the more than 105 different DNAs comprise human genomic
[Truncated to input limit]