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 .
Claim Status
Claims 3, 5-16, 18 and 72 are amended.
Claims 19-52, 54-71 and 73-94 are cancelled.
Claims 1-18, 53 and 72 are being examined.
Specification
The use of the terms “Phusion”, “New England Biolabs”, “Complete Genomics” and others, which are trade names or a marks used in commerce, has been noted in this application. The terms should be accompanied by the generic terminology; furthermore the terms should be capitalized wherever they appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Objections
Claims 1 and 53 are objected to because of the following informalities:
Claims 1 and 53 are missing commas following the words “comprises and 3’ in the following section: “template comprises continuously from 5' to 3' an upstream sequence and a probe binding sequence”. Appropriate correction is required.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-5, 7, 53 and 72 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Jia et al (2014; NPL C3 on IDS dated 05/22/2024).
Regarding claim 1, Jia et al teaches a composition with DNA target, DNA polymerase and a non-extensible oligonucleotide blocker (e.g., Jia et al., page 8, left column, paras 2-3) reading on the limitation “A composition comprising a DNA template, a DNA polymerase, and a non- extensible oligonucleotide” of the instantly rejected claim 1. Jia et al teaches the blocker as having a binding sequence that is fully complementary to a sequence on the DNA target (e.g., Jia et al., page 2, left column, para 3), and a stem where each strand is complementary to the other, and a loop positioned between the two stem sequences (e.g., Jia et al. Figure 1) reading on the limitations “wherein the non-extensible oligonucleotide comprises from 5' to 3':a binding sequence that is at least 70% identical to the reverse complement of the probe binding sequence of the DNA template, and a terminator hairpin” and “a first stem sequence, a second stem sequence, wherein the second stem sequence is the reverse complement of the first stem sequence, and a first loop sequence positioned between the first stem sequence and the second stem sequence” of the instantly rejected claim 1. Jia et al teaches a DNA target with blocker binding sequence that is complementary to the blocker, and an upstream sequence (e.g., Jia et al., page 7, left column, last para: underlined sections represent blocker binding sequence), reading on the limitation “wherein the DNA template comprises continuously from 5' to 3' an upstream sequence and a probe binding sequence” of the instantly rejected claim 1.
Regarding claim 2, Jia et al teaches that the blocker binding sequence is between 17 and 18 nucleotides long (e.g., Jia et al., page 7, left column, last para: underlined sections represent blocker binding sequence).
Regarding claim 3, Jia et al teaches that the loop sequence on the blocker is the reverse complement of the of the blocker binding sequence, not the reverse complement of the upstream sequence of the DNA target (e.g., Jia et al., page 7, left column, last para: underlined sections represent blocker binding sequence).
Regarding claim 4, Jia et al teaches that the blocker is the complement to the blocker binding sequence on the DNA target, and as such, does not hybridize to the upstream sequence of the DNA target (e.g., Jia et al., left column, last para: underlined sections represent blocker binding sequence).
Regarding claim 5, Jia et al teaches that the first and second stem sequences of the blocker are of equal length and may be between 3 and 8 nucleotides long (e.g., Jia et al., Table 1; Figure 1).
Regarding claim 7, Jia et al teaches that the first and second stem sequences of the blocker are of equal length and may be between 3 and 8 nucleotides long (e.g., Jia et al., Table 1; Figure 1).
Regarding claim 53, Jia et al teaches a non-extensible blocking oligonucleotide (i.e., blocker), that contains a binding sequence that is fully complementary to the binding sequence on a target DNA template, and stem sequences that are complementary to each other, but non-complementary to the target DNA template (e.g., Jia et al., page 2, left column, para 3; Figure 1). The blocker of Jia et al has a tail that is not complementary to the upstream sequence of the DNA template and does not hybridize to it (e.g., Jia et al., Figure 4).
Regarding claim 72, Jia et al teaches a method that includes a PCR amplification of a DNA template with a target sequence. The PCR includes the blocker specific to the DNA target, the limiting primer, the excess primer, DNA polymerase, the DNA target template and dNTPs and subjecting the mixture to 55 cycles of thermal cycling (e.g., page 8, left column, paras 2-3).
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-9, 12, 53 and 72 are rejected under 35 U.S.C. 103 as being unpatentable over Jia et al (2014; NPL C3 on IDS dated 05/22/2024) as applied to claims 1-5, 7, 53 and 72 above, and in view of Lamoureux et al (2006; published 1 August 2006).
Jia et al anticipates the composition of a DNA template, DNA polymerase and a non-extensible oligonucleotide of the instantly rejected claims 1-5, 7, 53 and 72 upon which claims 6, 8, 9 and 12 depend. Jia et al does not teach the DNA hairpin stem sequences of 4 nucleotides in length and having sequences GTTC and GAAC, but these were known in the art and were taught by Lamoureux et al.
Regarding claim 6, Lamoureux et al teaches DNA hairpin with complementary stem loop sequences of four nucleotides in length (i.e., 5’- GTTC-GAAC-3’) (e.g., Lamoureux et al., title; page 85, right column, para 1).
Regarding claim 8, Lamoureux et al teaches DNA hairpin with complementary stem loop sequences of four nucleotides in length (i.e., 5’- GTTC-GAAC-3’) (e.g., Lamoureux et al., title; page 85, right column, para 1).
Regarding claim 9, Lamoureux et al teaches DNA hairpin with complementary stem loop sequences of four nucleotides in length (i.e., 5’- GTTC-GAAC-3’) (e.g., Lamoureux et al., title; page 85, right column, para 1).
Regarding claim 12, Lamoureux et al teaches DNA hairpin with complementary stem loop sequences of four nucleotides in length (i.e., 5’- GTTC-GAAC-3’) (e.g., Lamoureux et al., title; page 85, right column, para 1).
It would have been prima facie obvious before the effective filing date of the claimed invention for a person having ordinary skill in the art to have used the well-known hairpin stem 5’- GTTC-GAAC-3’, of Lamoureux et al with the non-extensible oligonucleotide with hairpin and stem of Jia et al. The skilled artisan would have been motivated to use the hairpin stem sequences of Lamoureux et al, because different stem sequences affect the melting temperature, structure, and bond strength of the hairpin itself, and as such, can be tailored to match the thermal requirements of the nucleic acid protocol and by the teachings of Lamoureux et al that their stem sequences had the weakest h bond and resulted in a less stable and compact structure compared to others tested (e.g., Lamoureux et al., page 91, table 4; page 90, right column, first para). Thus, the addition hairpin stem of Lamoureux et al to the non-extensible oligonucleotide hairpin of Jia et al would have been a simple combination of known methods to yield predicable results and a skilled artisan would know to tailor their nucleic acid reagents to the needs of their protocol.
Claims 1-5, 7, 10, 13-15, 53 and 72 are rejected under 35 U.S.C. 103 as being unpatentable over Jia et al (2014; NPL C3 on IDS dated 05/22/2024) as applied to claims 1-5, 7, 53 and 72 above, and in view of Khutsishvili et al (2020; published 16 February 2020).
Jia et al anticipates the composition of a DNA template, DNA polymerase and a non-extensible oligonucleotide of the instantly rejected claims 1-5, 7, 53 and 72, upon which claims 10 and 13-15 depend. Jia et al does not teach the DNA hairpin loop sequence of 4 nucleotides in length and having sequence GCAA, but these were known in the art and were taught by Khutsishvili et al.
Regarding claim 10, Khutsishvili et al teaches a hairpin loop of 5’-GCAA-3’, having an adenine at the 3’ end (e.g., Khutsishvili et al., title).
Regarding claim 13, Khutsishvili et al teaches a hairpin loop of 4 nucleotides (e.g., Khutsishvili et al., title; page 66a, left column, para 1).
Regarding claim 14, Khutsishvili et al teaches a hairpin loop of 4 nucleotides (e.g., Khutsishvili et al., title; page 66a, left column, para 1).
Regarding claim 15, Khutsishvili et al teaches a hairpin loop of 4 nucleotides and having the sequence GCAA (e.g., Khutsishvili et al., title; page 66a, left column, para 1).
It would have been prima facie obvious before the effective filing date of the claimed invention for a person having ordinary skill in the art to have used the loop sequence of Khutsishvili et al with the non-extensible oligonucleotide with hairpin and stem of Jia et al. The skilled artisan would have been motivated to use the loop sequence of Khutsishvili et al because different loop sequences affect the melting temperature, structure, and bond strength of the hairpin, and as such, can be tailored to match the thermal requirements of the nucleic acid protocol and by the teachings of Khutsishvili et al that their experimentation of altering the hairpin loop sequence impacted the thermal stability of the structure, and that GCAA yielded generally higher melting temperatures, but the overall stability of the hairpin and stem structure were affected by the loop sequence, as well as the stem sequence it was paired with (e.g., Khutsishvili et al., page 66a, right column, para 1). Thus, the addition hairpin loop of Khutsishvili et al to the non-extensible oligonucleotide hairpin of Jia et al would have been a simple combination of known methods to yield predicable results and a skilled artisan would know to tailor their nucleic acid reagents to the needs of their protocol.
Claims 1-5, 7, 11, 53 and 72 are rejected under 35 U.S.C. 103 as being unpatentable over Jia et al (2014; NPL C3 on IDS dated 05/22/2024) as applied to claims 1-5, 7, 53 and 72 above, and in view of Lamoureux et al (2006; published 1 August 2006) in further view of Zhang (WO 2012/058488).
Jia et al anticipates the composition of a DNA template, DNA polymerase and a non-extensible oligonucleotide of the instantly rejected claims 1-5, 7, 53 and 72, upon which claim 11 depends. Jia et al in view of Lamoureux et al renders obvious the complementary stem sequence that is four nucleotides in length as described in the rejections above. Jia et al and Lamoureux et al do not teach the hairpin loop having an adenine at the 3’ end nor the stem sequences of TCTC and GAGA, but these were known in the art and were taught by Zhang.
Regarding claim 11, Lamoureux et al teaches a DNA hairpin with complementary stem loop sequences of four nucleotides in length (e.g., Lamoureux et al., title; page 85, right column, para 1). Zhang teaches a DNA hairpin with stem complementary sequences of 5’-TCTC-3’ and 5’-GAGA-3’ (e.g., Zhang Fig 6).
It would have been prima facie obvious before the effective filing date of the claimed invention for a person having ordinary skill in the art to have used the complementary hairpin stem sequences of four nucleotides in length of Lamoureux et al, and the hairpin with stem complementary sequences of 5’-TCTC-3’ and 5’-GAGA-3’ of Zhang with the composition of Jia et al. The skilled artisan would have been motivated to use the hairpin sequences of Lamoureux et al and Zhang with the composition of Jia et al by the teachings of Lamoureux et al, that varying the stem sequences altered physical characteristics, bond strength and stem and hairpin structure (e.g., Lamoureux et al., page 91, table 4; page 90, right column, first para) and by the teachings of Jia et al that different stem lengths alter melting temperature and other characteristics of the hairpin and stem (e.g., Jia et al., Table 1) and a skilled artisan would understand that optimizing oligonucleotide length and sequence would lead to desired specific characteristics (i.e., melting temperature, bond strength etc.). Further Zhang teaches that melting temperatures vary from target to target (e.g., Zhang page 2, para 3) and that their hairpin primers are designed to bind with high specificity to only intended targets and provide a high degree of specificity even in high nucleic acid background systems (e.g., Zhan page 3, para 1). Thus, the addition of the hairpin sequences of Lamoureux et al and Zhang to the composition of Jia et al would have been a simple combination of known methods to yield predicable results.
Claims 1-5, 7, 16-18, 53 and 72 are rejected under 35 U.S.C. 103 as being unpatentable over Jia et al (2014; NPL C3 on IDS dated 05/22/2024) as applied to claims 1-5, 7, 53 and 72 above, and in view of Smolke (US Patent 8772464, patented 8 July 2014).
Jia et al anticipates the composition of a DNA template, DNA polymerase and a non-extensible oligonucleotide of the instantly rejected claims 1-5, 7, 53 and 72 upon which claims 16-18 depend. Jia et al does not teach the oligonucleotide comprising a second hairpin between the binding sequence and the terminal hairpin, but these were known in the art and were taught by Smolke (US Patent 8772464, patented 8 July 2014).
Regarding claim 16, Smolke teaches an oligonucleotide comprising two hairpin structures, with a terminal hairpin and a middle hairpin that is between the terminal hair pin and the binding sequence, where each hairpin has complementary stem sequences (e.g., Smolke Fig. 8A), reading on the limitations “oligonucleotide further comprises a middle hairpin positioned between the binding sequence and the terminator hairpin, the middle hairpin comprising: a third stem sequence, a fourth stem sequence, wherein the fourth stem sequence is the reverse complement of the third stem sequence, and a second loop sequence positioned between the third stem sequence and the fourth stem sequence” of the instantly rejected claim 16.
It would have been prima facie obvious before the effective filing date of the claimed invention for a person having ordinary skill in the art to have used the multiple hairpin oligonucleotide of Smolke with the composition of Jia et al. The skilled artisan would have been motivated to use the multiple hairpin oligonucleotide of Smolke based on the teachings of Smolke that their invention can be designed for use in hybridization-dependent detection assays and are useful for detecting the presence, absence or amount of an analyte (e.g., Smolke column 2, lines 26-30). Thus, the addition of the dual-hairpin oligonucleotide of Smolke to the composition of Jia et al would have been a simple combination of known methods to yield predicable results.
Regarding claim 17, Jia et al teaches that the blocker hairpin oligonucleotide B1 has a 3’ final nucleotide of cytosine (e.g., Jia et al., page 6, right column, para 4).
Regarding claim 18, Jia et al teaches the stem sequences of the blocker can be between 3 and 8 nucleotides (e.g., Jia et al., Table 1; Figure 1; Page 7, right column para 2).
Conclusion
No claims allowed.
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/G.Y./Examiner, Art Unit 1683
/ANNE M. GUSSOW/Supervisory Patent Examiner, Art Unit 1683
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