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 .
Please note: The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
This Office Action is in reply to Applicants’ correspondence of 5/27/2026. Applicants’ remarks and amendments have been fully and carefully considered but are not found to be sufficient to put this application in condition for allowance. New grounds of rejection, necessitated by amendments, are presented in this Office Action. Any rejections or objections not reiterated herein have been withdrawn in light of the amendments to the claims or as discussed in this Office Action. This Action is FINAL.
Claim Status
Claims 1, 3-4, 6-7, and 9-10 are pending.
Claim 9 remains withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 1, 3-4, 6-7, and 10 are being examined on the merits.
Claim Objections
The objections to claims 1 and 10 are withdrawn in light of Applicant’s amendments to the claims.
Claim Rejections - 35 USC § 112b - Indefiniteness
Withdrawn Rejections
The rejection of claims 1-4, 6-8, and 10-13 under 35 U.S.C. 112(b) as detailed in the Office Action of 2/27/2026 is withdrawn in light of Applicant’s amendments to the claims and the cancellation of claims 2, 8, and 11-13.
New Rejections, Necessitated by Amendments
Claims 1, 3-4, and 6-7 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.
Claim 1 recites the limitations "a 5’ end universal amplification primer" in line 27 and “a 3’ end universal amplification primer” in line 35. Claim 1 also contains limitations directed to a primer pair of a first primer and a second primer, which are used to amplify the third probe (made up of the first and second probes ligated together. It is unclear if these universal amplification primers that the first probe is complementary to as stated in Formula II and the second probe is complementary to as stated in Formula III are the same primers as those described in the primer set from part (e). For the purposes of examination, these are interpreted as being the same primers, meaning the first and second primers of the primer pair have to be universal amplification primers in order to be the same ones as used for amplification of the third probe structure. However, further clarification is required.
Claims 3-4 and 6-7 depend from claim 1, inherit these deficiencies, and are rejected on the same basis.
Response to Remarks
While the amendments to claim 1 regarding the lack of antecedent basis issues as detailed in the Office Action of 2/27/2026 are resolved in the most recent amendments, new issues of indefiniteness have arisen as the result of said amendments and are addressed above.
Claim Rejections - 35 USC § 112d – Failure to Further Limit
The rejection of claim 11 under 35 U.S.C. 112(d) is withdrawn in light of Applicant’s cancellation of the claim.
Claim Interpretation
Regarding claim 5: In the interest of compact prosecution, the examiner is interpreting the subsequent limitations in the following way. “None” (“B3 is none”) is being interpreted to mean that the segment is not necessary to the structure of the quenching product capturing nucleic acid, and therefore the structure of Formula I could be: B0-B1-B2-B3 or B0-B1-B2.
New Claim Rejections - 35 USC § 103
Necessitated by Amendments
Withdrawn:
The rejection of claims 1, 3-4, 6-8, and 11-13 under 35 U.S.C. 103 as being unpatentable over Wenz et al. (US 2004/0110134 A1, published June 10, 2004; cited on PTO-892 of 2/26/2025) in view of Hassibi et al. (US 2017/0362648 A1, published December 21, 2017; cited on PTO-892 of 2/26/2025) and Guo et al. (Nucleic Acids Research, 1994; cited on PTO-892 of 2/27/2026) is withdrawn in light of Applicant’s amendments to the claims and cancellation of claims 8 and 11-13.
New (Necessitated by Amendments):
Claims 1, 3-4, and 6-7 are rejected under 35 U.S.C. 103 as being unpatentable over Wenz et al. (US 2004/0110134 A1, published June 10, 2004; cited on PTO-892 of 2/26/2025) in view of Hassibi et al. (US 2017/0362648 A1, published December 21, 2017; cited on PTO-892 of 2/26/2025) and Guo et al. (Nucleic Acids Research, 1994; cited on PTO-892 of 2/27/2026).
Wenz et al. teaches a system for quantitating target nucleic acids using ligation-dependent amplification and subsequent hybridization of amplicons to probes attached to a solid support (Abstract).
Regarding to claim 1: Wenz et al. teach a quantitative PCR which employs ligation-dependent amplification of target nucleic acids which are then detected through binding to a probe attached to a solid support at an addressable location. Specifically, Wenz et al. teach generation of a microarray (solid phase carrier) provided with n sub-detection regions, wherein n is a positive integer >= 2, and at least one sub-detection region is a surface quantitation sub-detection region…[which] is independently immobilized with a capture oligonucleotide (paragraph [0085], Figure 14). Wenz et al. teach a first probe, a second probe (“the probe set comprises (a) at least one first probe, comprising a first target-specific portion, and (b) at least one second probe, comprising a second target-specific portion and a 3' primer-specific portion”; paragraph [0006]), a ligase for connecting the first probe and the second probe to form the third probe (paragraph [0007] and [0056]), and a primer pair for amplifying the third probe (at least one primer set…to generate a first amplification product; paragraph [0007]).
Wenz et al. teaches that the structure of the first probe is X2’-T2’ (II) wherein, X2’ is a reverse complement of a 5’ end universal amplification primer and T2’ is a reverse complement of the specific sequence at the 5’ end of a targeting gene (Figure 3B and paragraph [0129]; “The first probe 22 further comprises a 5' primer-specific portion (5') and a target-specific portion 15a”). Wenz et al. specifically teach the 5’ end of the first probe is a “universal priming sequence” (paragraph [0233]).
Wenz et al. teaches that the structure of the second probe is T1’-P1’-X1’ (III) wherein, T1’ is a reverse complement of the specific sequence at the 3’ end of the targeting gene; P1’ is a barcode index sequence of a marker gene amplification combination; and X1’ is a reverse complement of a 3’ end universal amplification primer (Figure 3B and paragraph [0129]; “the second probe 23 comprises a target-specific portion 15b, an addressable support-specific portion 4, and a 3' primer-specific portion”). Wenz et al. specifically teach the 3’ end of the second probe is a “universal priming sequence” (paragraph [0233]). The “addressable support-specific portion” reads on P1’, as a barcode that is specific to the target gene and allows identification of the target gene amplification product when hybridized with the surface probe (paragraph [0068] and Figure 3).
Wenz et al. teach a capture oligonucleotide (quenching product capturing nucleic acid) with the formula B0-B2. Wenz et al. teaches that the 5’ end of the capture oligonucleotide consists of “a 5’ amino linker” (paragraph [0265]). In addition, the capture oligonucleotides were “24mers”, indicating that they contained a 24nt sequence complementary to the sequence of the target nucleic acid amplification product generated through ligation-dependent amplification (paragraph [0265] and Figures 2 and 3). Wenz et al. teach that the quenching product capturing nucleic acid specifically binds with the quenching target nucleic acid amplification product through complementary pairing between the capture region (P1) and the “addressable support-specific portion” reads on P1’, which is used as a barcode that is specific to the target gene and allows identification of the target gene amplification product when hybridized with the surface capture probe (paragraph [0068] and Figure 3).
As noted above, Wenz et al. teaches the structure of the first probe is X2’-T2’ (II) wherein, X2’ is a reverse complement of the 5’ end universal amplification primer and T2’ is a reverse complement of the specific sequence at the 5’ end of a targeting gene (Figure 3B and paragraph [0129]; “The first probe 22 further comprises a 5' primer-specific portion (5') and a target-specific portion 15a”), and the structure of the second probe is T1’-P1’-X1’ (III) wherein, T1’ is a reverse complement of the specific sequence at the 3’ end of the targeting gene; P1’ is a barcode index sequence of a marker gene amplification combination; and X1’ is a reverse complement of the 3’ end universal amplification primer (Figure 3B and paragraph [0129]; “the second probe 23 comprises a target-specific portion 15b, an addressable support-specific portion 4, and a 3' primer-specific portion”). Wenz et al. teaches that the first and second probe are ligated together to generate a ligation product (third probe) which now has the structure of X2’-T2’- T1’-P1’-X1’ (Figure 3C).
Wenz et al. does not teach wherein the detection system is an integrated single unitary system and comprises the following components…altogether, wherein at least one of the first primer and the second primer is a quenching primer, or that one end or one side of the quenching primer is connected with a quencher (claim 1). Wenz et al. does not teach the capture oligonucleotide immobilized to the solid phase carrier surface as having a first detectable marker selected from the group consisting of a fluorophore, a chemiluminescent label, a quantum dot, and a combination thereof or that the quenching amplification product generated by the quenching primer through amplification and at least one of the quenching product capturing nucleic acid of the surface quantitation sub-detection region can be combined to form a double-stranded structure and in the double-stranded structure, the quencher of the quenching amplification product causes the signal of the first detectable marker of the capturing nucleic acid to be quenched; the quencher is labeled at the 5’ end of the quenching amplification product (claim 1). However, amplification of nucleic acids using quenching primers and use of surface-immobilized probes containing a fluorophore which is quenched upon binding of the quenching amplification product within a single unitary detection system was known in the art, as taught by Hassibi et al.
Hassibi et al. teach an array comprising a solid support having a surface and a plurality of different probes, the different probes immobilized to the surface at different addressable locations, each addressable location comprising a fluorescent moiety; a PCR primer for each nucleic acid sequence that comprises a quencher; whereby amplified molecules hybridize with probes, thereby quenching signal from the fluorescent moiety (paragraph [0023]). Hassibit et al. teach that the detection system is a single unitary system in which all components are held in contact with one another (paragraphs [0193 and 0223]). Hassibi et al. teach that the detectable marker attached to one end of the quenching product capturing nucleic acids includes “small molecules, fluorescent proteins, and quantum dots” (paragraph [0167]). Hassibi et al. teach this quencher “is…at the 5’ end of the primer.” Amplification of the target nucleic acids produces “amplicons which contain quenchers” at the “5’ end of the amplicon” which hybridize with the fluorescent moiety-containing probe immobilized to the surface of the solid phase carrier (paragraphs [0086 and 0125]), form a double-stranded DNA structure and “results in a change in signal” due to quenching of the fluorophore (paragraph [0129] and Figure 1). Hassibi et al. also teach that the quenching product capturing nucleic acids contains a sequence that is complementary to a nucleic acid target sequence in an analyte, which enables hybridization between the capture probe and the target analyte (this reads on P1’ and P1).
It would have been prima facie obvious to one having ordinary skill in the art, before the effective filing date of the instant application, to have modified the method of Wenz et al. with Hassibi et al. One would be motivated to combine with Hassibi et al. because Hassibi et al. teach that their system of quenching amplification product and quenching product capturing nucleic acid with a fluorophore allows detection of real-time characteristics of affinity-based assays (Abstract). Hassibi et al. teach that integration of all components into a single system is advantageous given that one does not have to wash out fluid when in contact with the solid substrate while being able to obtain measurements of fluorescent signals at multiple time points (paragraph [0037]). Additionally, Hassibi et al. teach that this allows for real time measuring of fluorescent changes (paragraph [0077]). One would have a reasonable expectation of success given that Hassibi et al. successfully perform a qPCR detection reaction based on hybridization analysis between a fluorophore-labelled surface-immobilized probe and a quencher labelled amplified analyte.
Wenz et al. teach a capture oligonucleotide (quenching product capturing nucleic acid) with the formula B0-B2. Wenz et al. teaches that the 5’ end of the capture oligonucleotide consists of “a 5’ amino linker” (paragraph [0265]). In addition, the capture oligonucleotides were “24mers”, indicating that they contained a 24nt sequence complementary to the sequence of the target nucleic acid amplification product generated through ligation-dependent amplification (paragraph [0265] and Figures 2 and 3). Wenz et al. in view of Hasibi et al. do not teach that the quenching product capturing nucleic acid (or capture oligonucleotide) contains B1 within the structure, a flexible transition region consisting of a flexible transition nucleic acid fragment with a length of 1-100 nt. However, use of flexible transition regions made of nucleic acids in surface immobilized capture oligonucleotides is known in the art, as taught by Guo et al.
Guo et al. teach a method of allele-specific hybridization between PCR amplified product and a surface-bound oligonucleotide array (Abstract). Guo et al. teaches that the surface-bound oligonucleotide contains a 5’-amino modified linker region that links the oligonucleotide to the array surface, a flexible transition spacer region consisting of 15 dT nucleotides (Figure 1; 15 nt reads on 1-00 nt).
It would have been prima facie obvious to one having ordinary skill in the art, before the effective filing date of the instant application, to have modified the system of Wenz et al. in view of Hasibi et al. with the teachings of Guo et al. One would be motivated to include the spacer region (flexible transition region) as taught by Guo et al. given the assertion by Guo et al. that inclusion of a spacer increased hybridization efficiency between amplification products and the surface-bound oligonucleotides through removal of steric interference with the support surface (pg 5460, col 1, paragraph 3). One would have a reasonable expectation of success given that Guo et al. successfully constructs a surface-immobilized oligonucleotide with a linking group, flexible transition region, and a capture region that readily binds to complementary amplification products in solution (Figure 3).
Regarding claim 3: Wenz et al. teach that the 5’ end universal primer sequence of the first probe (X2’) is 21nt (within the range of 15-50nt; paragraph [0233] and Table 2(I) on page 24).
Regarding claims 4 and 6-7: Wenz et al. teach “the length of…[the] target-specific portion” as 12-35nt (reads on T2’ is 15-60nt and T1’ is 15-60nt). Wenz et al. teach a specific example in which the T2’ and T1’ portions of the first and second probes is 15nt for each probe (RPS4x probes, T-SP are the capital letters not in a box; Table 2(I)). Wenz et al. teach an addressable-support specific sequence (reads on P1’) which is 12-35nt long (reads on 10-500nt). In a specific example that Wenz et al. provides, they teach a P1’ region that is 24nt long (paragraph [0233] and Table 2(I)).
In addition, regarding the lengths claimed in claims 4 and 6-7, it is noted that the courts have stated where the claimed ranges “overlap or lie inside the ranges disclosed by the prior art” and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists (see In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990); Titanium Metals Corp. of America v. Banner, 778 F2d 775. 227 USPQ 773 (Fed. Cir. 1985) (see MPEP 2144.05.01).
It is noted that the courts have found that “where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05 II. Thus, the claimed ratio merely represents routine optimization of the hybridization distance.
Therefore, the claimed ranges merely represent an obvious variant and/or routine optimization of the values of the cited prior art.
Applicant is advised that MPEP 716.01(c) makes clear that “[t]he arguments of counsel cannot take the place of evidence in the record” (In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965)). Thus, Applicant should not merely rely upon counsel’s arguments in place of evidence in the record.
Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Wenz et al. (US 2004/0110134 A1, published June 10, 2004; cited on PTO-892 of 2/26/2025) in view of Hassibi et al. (US 2017/0362648 A1, published December 21, 2017; cited on PTO-892 of 2/26/2025).
Wenz et al. teach quantitative PCR which employs ligation-dependent amplification of target nucleic acids which are then detected through binding to a probe attached to a solid support at an addressable location. Specifically, Wenz et al. teach generation of a microarray (solid phase carrier) provided with n sub-detection regions, wherein n is a positive integer >= 2, and at least one sub-detection region is a surface quantitation sub-detection region…[which] is independently immobilized with a capture oligonucleotide (paragraph [0085], Figure 14). Wenz et al. teach a first probe, a second probe (“the probe set comprises (a) at least one first probe, comprising a first target-specific portion, and (b) at least one second probe, comprising a second target-specific portion and a 3' primer-specific portion”; paragraph [0006]), a ligase for connecting the first probe and the second probe to form the third probe (paragraph [0007] and [0056]), and a primer pair for amplifying the third probe (at least one primer set…to generate a first amplification product; paragraph [0007]).
Wenz et al. teaches packaging necessary reagents for their quantitative PCR described above packaged into a kit “designed to expedite performing the subject methods” (paragraph [0224]). Wenz et al. teaches including “components in pre-measured unit amounts” (reads on containers). As detailed above, Wenz et al. teach a solid support provided with n sub-detection regions each independently immobilized with a capture oligonucleotide (quenching product capturing nucleic acid that is single-stranded), a first probe, a second probe, a ligase, a primer set, and an amplification product capable of creating a double-stranded structure with the capture oligonucleotide. All of these components would be advantageous to include in the kit for the reason asserted by Wenz et al. above. Wenz et al. also teach inclusion of a buffer or buffer component for PCR amplification, a polymerase for PCR amplification, and instructions (paragraph [0227]).
Wenz et al. does not teach wherein at least one of the first primer and the second primer is a quenching primer, or that one end or one side of the quenching primer is connected with a quencher. Wenz et al. does not teach that the capture oligonucleotide immobilized to the solid phase carrier surface as having a first detectable marker selected from the group consisting of a fluorophore, a chemiluminescent label (luminescent label), and a quantum dot or that the quenching amplification product generated by the quenching primer through amplification and at least one of the quenching product capturing nucleic acid of the surface quantitation sub-detection region can be combined to form a double-stranded structure and in the double-stranded structure, the quencher of the quenching amplification product causes the signal of the first detectable markers of the capturing nucleic acid to be quenched. However, amplification of nucleic acids using quenching primers and use of surface-immobilized probes containing a fluorophore which is quenched upon binding of the quenching amplification product within a single unitary detection system was known in the art, as taught by Hassibi et al.
Hassibi et al. teach an array comprising a solid support having a surface and a plurality of different probes, the different probes immobilized to the surface at different addressable locations, each addressable location comprising a fluorescent moiety; a PCR primer for each nucleic acid sequence that comprises a quencher; whereby amplified molecules hybridize with probes, thereby quenching signal from the fluorescent moiety (paragraph [0023]). Hassibit et al. teach that the detection system is a single unitary system in which all components are held in contact with one another (paragraphs [0193 and 0223]). Hassibi et al. teach that the detectable marker attached to one end of the quenching product capturing nucleic acids includes “small molecules, fluorescent proteins, and quantum dots” (paragraph [0167]). Hassibi et al. teach this quencher “is at the 3’ end of the primer [or] at the 5’ end of the primer.” Amplification of the target nucleic acids produces “amplicons which contain quenchers” at the “5’ end of the amplicon” which hybridize with the fluorescent moiety-containing probe immobilized to the surface of the solid phase carrier (paragraphs [0086 and 0125]), form a double-stranded DNA structure and “results in a change in signal” due to quenching of the fluorophore (paragraph [0129] and Figure 1). Hassibi et al. also teach that the quenching product capturing nucleic acids contains a sequence that is complementary to a nucleic acid target sequence in an analyte, which enables hybridization between the capture probe and the target analyte (this reads on P1’ and P1).
It would have been prima facie obvious to one having ordinary skill in the art, before the effective filing date of the instant application, to have modified the kit of Wenz et al. with the teachings of Hassibi et al. One would be motivated to combine with Hassibi et al. because Hassibi et al. teach that their system of quenching amplification product and quenching product capturing nucleic acid with a fluorophore allows detection of real-time characteristics of affinity-based assays (Abstract). Additionally, Hassibi et al. teach that this allows for real time measuring of fluorescent changes (paragraph [0077]). One would have a reasonable expectation of success given that Hassibi et al. successfully perform a qPCR detection reaction based on hybridization analysis between a fluorophore labelled surface-immobilized probe and a quencher labelled amplified analyte.
Response to Remarks
Applicant's arguments filed 5/27/2026 have been fully considered but they are not persuasive for the following reasons.
Applicant has traversed the rejection of claims 1, 3-4, 6-8, and 10-13 as obvious over Wenz et al. in view of Hasibi et al and Guo et al. (pg 7-16). As noted above, the rejection as presented in the Office Action of 2/27/2026 has been withdrawn in light of Applicant’s amendment to the claims and cancellation of claims 8 and 11-13. New rejections have been made above and Applicant’s arguments relevant to said new rejections are addressed below.
Applicant asserts that “the Office has overlooked the different technical effects between the presently claimed systems/methods and those taught in the cited references” (pg 8 of Remarks). In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., amplification and signal detection occurring simultaneously, i.e., real-time quantitative PCR) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). The claims do not recite any limitations which require simultaneous amplification and signal detection.
Applicant argues that the methodology of Wenz is specifically directed to end point detection wherein hybridization is performed after amplification is completed (pg 9 of Remarks). First, as noted above, the claims as currently written do not require simultaneous amplification and signal detection. Second, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Wenz is relied upon for their teachings regarding ligation-dependent amplification and hybridization to surface immobilized probes.
Applicant argues that Hassibi teaches a classical type of PCR, rather than ligation dependent amplification, does not teach barcode sequences but rather teaches target-specific hybridization between the amplification product and immobilized probe, and does not provide specific advantages as supplied by the current methodology (pg 9-12 of Remarks). First, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Hassibi is relied upon for their teachings of creating amplification products that contains quenchers which then hybridize to immobilized probes which contain a fluorophore that is quenched upon binding of said quenching amplification product. As noted by applicant, Hassibi teaches that the amplification product has a quencher at the 5’ end and the immobilized probe has a fluorophore on the 3’ free end. Applicant then lists another embodiment of Hassibi that is different from the claimed invention in which the primer may carry a fluorophore rather than a quencher (pg 9 of Remarks). As noted by applicant, this is an alternative embodiment taught by Hassibi which does not in any way discourage or teach away from combining the quenching primer rather than the fluorophore primer with Wenz. Applicant’s arguments regarding what Hassibi does not teach (barcodes and barcode binding to immobilized probes, ligation-dependent amplification) are features which are taught and addressed by Wenz, as cited in the 103 rejections above. In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., minimization of false negative issues) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). Furthermore, the problems that applicant points out with the methodology of Hassibi et al. are inconsequential given that Hassibi et al. is modifying the teachings of Wenz et al. Wenz et al. overcomes issues such as target-specific amplification (use of first and second probes which are ligated to form a third probe with a barcode region and universal amplification regions) and false negative hybridization (use of barcodes; pg 13-14 of Remarks).
Applicant argues that the use of a universal primer system distinguishes the claimed invention from the cited prior art (pg 12-13 of Remarks). However, as noted in the 103 rejection above, Wenz does teach that universal primers can be used for amplification of the ligated probe product. Applicant even notes that Wenz teaches that the primers can be universal, therefore Wenz DOES teach that the targets can share the same pair of primers for simultaneous amplification (which is what universal means). Furthermore, Applicant is again arguing against Wenz and Hassibi individually (pg 12) and one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Applicant states that the “universal primer” feature is presently claimed in component (e) of claim 1. As noted in the 112b rejection of claim 1 above, claim 1(e) merely recites a primer pair and not a universal primer pair. Additionally, claim 1 does not require that there are multiple different targets.
Applicant argues that “the Office mischaracterizes Guo’s teachings” (pg 13 of Remarks). Applicant argues that “Guo at best teaches a poly-dT spacer”, does not mention any other type of spacer, and that optimization of the spacer is based on end-point hybridization signal intensity (pg 13-14 of Remarks). Applicant’s arguments do not provide any information or justification as to why a poly-dT spacer is different in any way from the claimed flexible transition nucleic acid fragment with a length of 1-100nt. It’s a region of an immobilized capture probe that is located between a linking group attaching a probe to a solid surface and a capture region used to hybridize to target molecules in solution. The specification does not provide any special definitions of a flexible transition region that would preclude a poly-dT spacer from being considered as such. In response to applicant's argument that Guo’s spacer is used to physically distance the capture region from the steric hindrance of the solid surface, the fact that the inventor has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985). Moreover, the increase of hybridization efficiency that the poly-dT spacer provides (as taught by Guo) is directly relevant to the methodology of Wenz in view of Hassibi, which rely on efficient hybridization of molecules in solution with a probe immobilized on a solid surface. Additionally, Applicants admit that the design of the flexible linker is for optimizing hybridization kinetics on pg 15, further making it unclear as to how the spacer of Guo is different. It is acknowledged that Guo does not mention any other type of flexible transition linker, however the claim as written only requires the presence of one type of flexible transition region (“a flexible transition region selected from the group consisting of”). Applicant argues that Guo does not teach real-time detection, barcodes, or quenching amplification products (pg 14 of Remarks). In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Guo is relied upon for their teaching regarding the flexible transition region.
Applicant argues that the combination of all three references does not “result…in the inventive concept of ‘ligation product (third probe) as the sole template, a single pair of universal primers amplifying all targets, and simultaneous amplification and hybridization’ of the presently claimed systems/methods” (pg 15-16). As noted in the 103 rejection above, all limitations of the present claims are taught by the cited references. And as noted above in previous responses to Applicant’s remarks, simultaneous amplification and hybridization is not a claimed feature of the present invention. Applicant asserts that Wenz does not teach a universal primer system, however as noted in this Office Action and in the previous Office Action of 2/27/2026, Wenz does teach the use of universal primers. Applicant concludes by arguing that there could be no reasonable expectation of success in combining said references (pg 16 of Remarks), but has not provided any arguments to refute the cited reasons for expectations of success as noted in the 103 rejection above.
For these reasons, the rejection of claims 1, 3-4, 6-7, and 10 under 35 USC 103 are maintained.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KAILEY E CASH whose telephone number is (571)272-0971. The examiner can normally be reached Monday-Friday 8:30am-6pm ET.
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/KAILEY ELIZABETH CASH/Examiner, Art Unit 1683
/STEPHEN T KAPUSHOC/Primary Examiner, Art Unit 1683
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