Office Action 2: Notice of Allowance (2025-02-18)

CLAIMS:
CLAIM AMENDMENTS

1\. (Currently amended) An array of polynucleotide molecules on a surface,wherein said surface comprises nucleotide binding regions separated by non-nucleotide binding regions arranged on the surface in a predetermined pattern;
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\. Cancelled

3\. (Original) The array of claim 1, wherein said nucleotide binding regions are discrete spaced apart regions.

4\. (Original) The array of claim 3, wherein said non-nucleotide binding regions are inter-regional areas that separate said discrete spaced apart regions.

5\. (Currently amended) The array of claim 1,wherein said nucleotide binding regions are arranged in a grid pattern.

6\. (Original) The array of claim 1, wherein said polynucleotide molecules are linear or branched.

7\. (Original) The array of claim 1, wherein more than 105 different polynucleotide molecules are present on the array.

8\. (Currently amended) The array of claim 1, wherein at least part of the sequence of each of said polynucleotide molecules attached on the nucleotide binding regions is not known.

9\. (Currently amended) The array of claim 8, wherein each of said polynucleotide molecules comprises a nucleotide sequence of genomic DNA, cDNA, or RNA.

10\. (Currently amended) The array of claim 1, wherein said nucleotide capture chemistry is a plurality of oligonucleotides in each nucleotide binding region that binds one of said polynucleotide molecules to each region.

11\. (Currently amended) The array of claim 10, wherein each oligonucleotide in each nucleotide binding region contains a nucleic acid sequence that is complementary to and hybridizes with said polynucleotide molecules.

12\. (Currently amended) The array of claim 11, wherein said nucleic acid sequence of the oligonucleotides in each nucleotide binding region is identical to nucleic acid sequences contained in oligonucleotides in other nucleotide binding regions.

13\. (Original) The array of claim 10, wherein said oligonucleotides are 20 to 100 bases in length.

14\. (Original) The array of claim 10, wherein said oligonucleotides are produced by nano-printing techniques, or by creating active sites for oligonucleotide attachment using photochemistry.

15\. (New) The array of claim 10, wherein-at least part of the sequence of each of said polynucleotide molecules attached on the nucleotide binding regions is not known.

16\. (New) The array of claim 15, wherein said oligonucleotides are directly attached to said surface,and said polynucleotide molecules comprising said unknown sequence are hybridized directly to said oligonucleotides.

17\. (New) An array of polynucleotide molecules on a surface,wherein said surface comprises nucleotide binding regions separated by non-nucleotide binding regions arranged on the surface to form a predetermined pattern;
wherein the nucleotide binding regions comprise nucleotide capture chemistry and the non- nucleotide binding regions do not have the nucleotide capture chemistry;
wherein the nucleotide binding regions in the array are occupied with a single one of the polynucleotide molecules;
wherein said surface is not a bead; and
wherein-at least part of the sequence of each of said polynucleotide molecules attached on the nucleotide binding regions is not known

18\. (New) The array of claim 17, wherein said nucleotide capture chemistry is a plurality of oligonucleotides in each nucleotide binding region that binds one of said polynucleotide molecules to each region.

19\. (New) The array of claim 18, wherein each oligonucleotide in each nucleotide binding region contains a nucleic acid sequence that is complementary to and hybridizes with said polynucleotide molecules.

20\. (New) The array of claim 19, wherein said nucleic acid sequence of the oligonucleotides in each nucleotide binding region is identical with nucleic acid sequences contained in oligonucleotides in other nucleotide binding regions.

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.

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


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.