DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Claims 18-27 are currently pending and herein discussed on their merits.
Priority
It is acknowledged that the instant application is a divisional of Patent Application No. 16/701,863, filed December 3, 2019, and that it claims benefit of provisional 62/780,602, filed December 17, 2018. The effective filing date is considered to be December 17, 2018.
Information Disclosure Statement
Information disclosure statements from 1) 12/11/23, 2) 5/1/24, 3) 1/21/25, and 4) 3/7/25 have been received. IDS entries from 12/11/23 and 5/1/24 have been crossed out and not considered, as they fail to comply with 37 CFR 1.98(a)(2), which requires a legible copy of each cited foreign patent document; each non-patent literature publication or that portion which caused it to be listed; and all other information or that portion which caused it to be listed. It has been placed in the application file, but the information referred to therein has not been considered.
Specification
Applicant is reminded of the proper content of an abstract of the disclosure.
A patent abstract is a concise statement of the technical disclosure of the patent and should include that which is new in the art to which the invention pertains. The abstract should not refer to purported merits or speculative applications of the invention and should not compare the invention with the prior art.
If the patent is of a basic nature, the entire technical disclosure may be new in the art, and the abstract should be directed to the entire disclosure. If the patent is in the nature of an improvement in an old apparatus, process, product, or composition, the abstract should include the technical disclosure of the improvement. The abstract should also mention by way of example any preferred modifications or alternatives.
Where applicable, the abstract should include the following: (1) if a machine or apparatus, its organization and operation; (2) if an article, its method of making; (3) if a chemical compound, its identity and use; (4) if a mixture, its ingredients; (5) if a process, the steps.
Extensive mechanical and design details of an apparatus should not be included in the abstract. The abstract should be in narrative form and generally limited to a single paragraph within the range of 50 to 150 words in length.
See MPEP § 608.01(b) for guidelines for the preparation of patent abstracts.
The abstract of the disclosure is objected to because it does not include process steps as set forth in the instant application’s invention. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 23-26 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 23 and 24 are rejected over the recitation of “…are attached during incorporation, potential application, and optical detection” in claim 23. It is not clear whether the labels as recited are being actively attached (i.e. attachment occurs during these steps), or if the labels are passively attached (i.e. the nucleotides are labeled prior to and remain attached during these steps). It is also not clear whether the unit composed of the label and linking molecule is attached to the nucleotide, or whether the label and linking molecule are attached to each other, or both, or some other interpretation. As a result, one of skill in the art would not be able to determine the metes and bounds of the claimed subject matter so as to avoid infringement.
Claim 25 is rejected as indefinite over the recitation of “an electrical signal that corresponds to the optical emission.” It is unclear from the language of the limitation whether the electrical signal results from or is caused by the optical emission, or whether it has some other correlation (i.e. both are simply related by some other shared factor). As a result, one of skill in the art would not be able to determine the metes and bounds of the claimed subject matter so as to avoid infringement.
Claim 26 is rejected as indefinite because although the claim only requires one of the four nucleotides to be incorporated, and does not state that the four nucleotides are present in the reaction, the method requires that a reagent cleave the label from the first nucleotide and add it to the third. If the first and/or third nucleotide is not present in the reaction, then the step requiring introduction of the reagent and all subsequent steps cannot occur. It is therefore unclear how the method would be implemented.
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 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.
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).
Claims 18-21, 23-25, and 27 are rejected under 35 U.S.C. 103 as unpatentable over the combination of Meuleman et al. (published April 4, 2013; Patent Publication No. US 2013/0085083) and Hou et al. (published November 3, 2016; Patent Publication No. US 2016/0318016). The rejection is further evidenced by Richter (published March 20, 2004; Richter. Chem Rev. 2004 Jun;104(6):3003-36).
Meuleman et al. teaches methods of sequencing nucleic acids including sequence-by-synthesis (par. 4).
Regarding claim 18, Meuleman recites introducing a fluid including a polymerase and nucleotides to a flow cell (par. 4, 61). Meuleman teaches that at least some of the nucleotides are labeled nucleotides having: a 3′ OH blocking group (par. 56), a linking molecule attached to a base or a sugar of the nucleotide, and an electrochemiluminescent label attached to the linking molecule (par. 89-90, 93). Meuleman recites the incorporation of one of the labeled nucleotides into a nascent strand complementary to the template polynucleotide chain and detecting an optical emissions (par. 4, 57).
Meuleman does not teach explicitly teach an optical emission in response to applied potential. However, Meuleman does teach distinguishing labeled nucleotides by the label’s electrical or luminescent properties (par. 57), as well as using electrochemiluminescent labels detected by methods known to those skilled in the art (par. 93). As evidenced by Richter, it would be known to a skilled artisan to apply potential and detect the resulting light emission when using electrochemiluminescent labels (pg. 3004, col 2, 1st full par.; pg. 3029, col 2).
Meuleman does not recite applying a potential to an electrode that partially defines a depression in a flow cell where the template is attached.
Hou teaches methods of using flow cells with electrodes for sequencing nucleic acids (Abstract), in which application of potential is used to affect polynucleotides (par. 31).
Regarding claims 18, Hou recites a flow cell which includes an electrode that partially defines a surface under an attached template polynucleotide chain (par. 7), where the surface is within a depression (par. 19: “immobilized in one or more wells”).
It would be obvious to one with ordinary skill in the art, before the effective filing date of the instant invention, to combine the method of Meuleman with the device of Hou, in order to detect labeled nucleotides through their electrical properties, as suggested in Meuleman (par. 57).
Regarding claim 19, Meuleman recites the incorporation of a labeled nucleotide into a nascent strand complementary to the template polynucleotide chain (par. 48).
Meuleman does not teach explicitly teach that the application of potential initiates a redox reaction pathway involving the label of the incorporated nucleotide. However, as evidenced by Richter, electrochemiluminescence is a means of converting electrical energy into light which involves initiation of redox reactions (pg. 3003: Principles of ECL). Therefore, by teaching electrochemiluminescent labels detected by methods known to those skilled in the art (par. 93), the limitation is met by Meuleman.
Regarding claim 20 and 21, Meuleman recites a fluid (par. 61) with at least three different labeled nucleotides (par. 143). Meuleman recites each label having a distinct optical emission spectrum used for identifying the incorporated nucleotides (par. 57, 143). Meuleman also recites identification by other means, including both optical and electrical properties (par. 57) and using electrochemiluminescent labels (par. 93), which is inclusive of the instant application’s limitation in claim 21 that the labels are identified using their distinct reduction oxidation properties relative to an applied potential.
Regarding claim 23, Meuleman recites the linking molecule and label being attached during incorporation, potential application, and optical detection (par. 88), as well as a deblocking agent which cleaves the label and 3’ OH blocking groups from the incorporated nucleotide (par. 89).
Regarding claim 24, Meuleman discloses fluidically replacing reagents multiple times in a traditional sequence-by-synthesis reaction (par. 77), thus the reference teaches introducing an other fluid. Meuleman recites applying an other stimulus and detecting an other optical emission (par. 117). As discussed above, although Meuleman does not explicitly discuss the application of potential to an electrode, such an embodiment is congruent with its teachings.
Regarding claim 25, Meuleman recites a photodiode detecting the optical emission and detection of a corresponding electrical signal (par. 146). Although Meuleman does not explicitly address a corresponding electrical signal, by definition photodiodes are devices that convert light into electrical current.
Regarding claim 27, Meuleman recites a plurality of sites where a plurality of template polynucleotide chains are attached, where nucleotides are incorporated into nascent strands complementary to template polynucleotides (par. 4, 61-62), and simultaneously detecting a respective optical emission from each of the plurality of sites (par. 121-122).
Claim 22 is rejected under 35 U.S.C. 103 as unpatentable over the combination of Meuleman et al. (published April 4, 2013; Patent Publication No. US 2013/0085083) and Hou et al. (published November 3, 2016; Patent Publication No. US 2016/0318016), as applied to claims 18 and 19 above, and further in view of Richter (published March 20, 2004; Richter. Chem Rev. 2004 Jun;104(6):3003-36). It is noted that the rejection of claims 18-19 was further evidenced by Richter.
Meuleman and Hou teach the limitations of claims 18 and 19, as discussed above.
Regarding claim 22, Meuleman and Hou do not recite a co-reactant introduced before the application of potential.
Richter discloses the properties and uses of electrochemiluminescence in biological applications (Introduction).
Regarding claim 22, Richter teaches the use of co-reactants in electrochemiluminescence (pg. 3008: Coreactant ECL). These co-reactants are present at the same time as the primary electrochemiluminescent species, and the electrode induces the redox reaction in a single potential step (pg. 3008, 1st full paragraph), thus meeting the limitation that a co-reactant is introduced prior to applying potential.
It would have been obvious to a person with ordinary skill in the art before the effective filing date of the instant invention, to combine the teachings of Meuleman and Hou with the teachings of Richter, in order to allow for the easy generation of electrochemiluminescence in aqueous solutions (pg. 3009, col. 2, fourth full par.).
Claim 26 is rejected under 35 U.S.C. 103 as unpatentable over the combination of Meuleman et al. (published April 4, 2013; Patent Publication No. US 2013/0085083) and Hou et al. (published November 3, 2016; Patent Publication No. US 2016/0318016), as applied to claim 18 above, and further in view of Kain et al. (published March 28, 2013; Patent Publication No. US2013/0079232) and Li et al. (published March 28, 2016; Li et al. Nat Chem Biol. 2016 Mar;12(3):129-37). It is noted that the rejection of claim 18 was further evidenced by Richter.
Meuleman and Hou teach the limitations of claim 18, as discussed above.
Regarding claim 26, Meuleman and Hou recite: a labeled nucleotide wherein the linking molecule is cleavable (Meuleman: par. 91); or a non-labeled nucleotide having a 3′ OH blocking group (Meuleman: par. 97).
Meuleman and Hou do not recite: a labeled nucleotide wherein the linking molecule is non-cleavable; a non-labeled nucleotide having a 3′ OH blocking group and including a linking molecule that is to attach to the label; or introducing a reagent that can cleave the label from the cleavable labeled nucleotide and add the label to the to-be-labeled nucleotide.
Kain teaches methods for detecting multiple different nucleotides in a sample (Abstract).
Regarding claim 26, Kain teaches nucleotides having a first labeled nucleotide, wherein the linking molecule is cleavable (par. 44: rbATP; note that ‘rb’ means the nucleotide is reversibly blocked), a second labeled nucleotide, wherein the linking molecule is not cleaved (par. 44: rbTTP), a third non-labeled nucleotide having a 3′ OH blocking group and including a linking molecule that is to attach to the label (par. 43-44: rbCTP), and a fourth non-labeled nucleotide having a 3′ OH blocking group (par. 43-44: rbGTP).
In this specific example, Kain teaches a second labeled nucleotide which is not cleaved but which nonetheless contains a cleavage group. However, in the description of this embodiment, Kain allows that labels may be attached to a nucleotide using a linker which has no cleavage groups (par. 43). Additionally, the cleavage group in the second nucleotide’s linker is not required for the general sequencing strategy laid out in the embodiment (Fig. 1, par. 43-53). Therefore, the limitation that the second nucleotide does not contain a cleavage group is considered to be met.
Kain does not teach that a single reagent is used to cleave the label from the first labeled nucleotide and add the label to the third non-labeled nucleotide.
Li et al. teaches bioorthogonal chemical reactions for investigating biological processes (Abstract).
Li teaches various agents which can be used in ‘ligation’ or attachment-type reactions to add functional groups/labels (Figure 1), and in cleavage-type reactions to remove functional groups/labels (Figure 2). These agents include ruthenium and copper, as well as non-chemical agents such as light, which Li teaches may be used to simultaneously accomplish both attachment and cleavage (pg. 135, col 1, 1st par.; Figure 6a, iii and iv).
It would be obvious, before the effective filing date of the instant invention, to combine the teachings of Meuleman, Hou, and Kain with the teachings of Li, in order to decage biomolecules for applications that need to be carried out in a precisely tunable manner (Li: pg.130, col. 2, 1st full par.).
Conclusion
No claims are allowed.
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/C.M.J./Examiner, Art Unit 1682
/AMANDA HANEY/Primary Examiner, Art Unit 1682