DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Application
2. Applicant's response filed on April 2, 2026 has been entered.
Claims 17, 19-28, 30-34, and 36-42 are pending and under examination.
Information Disclosure Statement
3. Applicant’s submission of an Information Disclosure Statement (IDS) on October 21, 2025; December 2, 2025; and January 7, 2026 is acknowledged.
All of the references cited on the IDSs of October 21, 2025 and January 7, 2026 have been considered.
Non-patent literature citation 1 on the IDS filed on December 2, 2025 has not been considered. In particular, this non-English document has not been considered because the IDS filed on December 2, 2025 fails to comply with 37 CFR 1.98(a)(3)(i) since it does not include a concise explanation of the relevance, as it is presently understood by the individual designated in 37 CFR 1.56(c) most knowledgeable about the content of the information, of each reference listed that is not in the English language.
Applicant is advised that the date of any re-submission of any item of information contained in the IDS of December 2, 2025 or the submission of any missing element(s) will be the date of submission for purposes of determining compliance with the requirements based on the time of filing the statement, including all certification requirements for statements under 37 CFR 1.97(e). See MPEP § 609.05(a).
Response to Arguments
4. Applicant's arguments filed on April 2, 2026 have been fully considered.
Objection to the Abstract
Applicant argues that the objection should be withdrawn because the abstract is actually less than 150 words in length (Remarks, page 6).
This argument was persuasive. The objection has been withdrawn.
Claim Objections
Applicant argues that the objections to claims 17, 24, and 34 should be withdrawn in view of the amendments to those claims (Remarks, page 6).
This argument was persuasive. The objections have been withdrawn.
Rejection of claims 18-22, 36, and 37 under 35 U.S.C. 112(a) (new matter)
Applicant argues that the rejection is moot with respect to claim 18 since that claim was canceled in the response of April 2, 2026 (Remarks, page 7). Applicant also argues that the new matter issue concerning claims 36 and 37 is also moot in view of the amendments to claim 17, from which claim 36 depends (Remarks, page 7).
These arguments were persuasive. The rejection has been withdrawn.
Rejection of claims 17-42 under 35 U.S.C. 112(a) (enablement)
Applicant presents several arguments regarding the rejection (Remarks, pages 8-11). These arguments have been fully considered with respect to the rejection, which is modified in view of the claim amendments, but they were not persuasive for the following reasons.
Argument:
Applicant first argues that the rejection should be withdrawn in view of the amendments to independent claim 17, which now requires particular dissociation conditions (Remarks, pages 8-9). Here, Applicant also argues that “[T]he claimed method relies on universal physical-chemical properties of ternary complex stability (e.g., non-covalent forces) that are common across the entire polymerase genus” (Remarks, page 9). In other words, Applicant argues, the particular polymerase and template nucleic acid “does not alter the underlying physical mechanism of the method” since the dissociation conditions “target the binding affinity of the nucleotide cognate” (Remarks, page 9).
Response:
These arguments have been fully considered, but they were not persuasive. First, although the amendments to independent claim 17 narrow the dissociation conditions relative to the last claim set, the genus of dissociation conditions is still very broad since it encompasses any organic solvent, does not place an upper limit on the organic solvent concentration, and encompasses any salt (or even no salt). Second, while it may be Applicant’s intention for the dissociation conditions to only target the binding affinity of the cognate nucleotide, the presence of an organic solvent and/or various salts may also have a detrimental effect on the polymerase and nucleic acid template. See, for example, the teachings throughout Nakano & Sugimoto (Biophysical Reviews 2016; 8: 11-23; newly cited) as well as the teachings throughout Elias et al. (ACS Synthetic Biology 2023; 12: 3170-3188; newly cited). Therefore, it is not, in fact, clear that the polymerase and/or template nucleic acid will be unaffected by the various dissociation conditions encompassed by the amended claims.
Argument:
Applicant also argues that the Dambacher, Turcatti, and Seo references cited in the rejection do not actually provide negative teachings or evidence of unpredictability against the claimed invention (Remarks, pages 9-10). As to Dambacher, Applicant argues that the reference’s teaching of alcohols as fluids that stabilize a ternary complex actually supports enablement of the current method since that teaching in Dambacher “confirms that polymerases remain stable and associated with the template in the presence of organic solvents” (Remarks, pages 9-10). As to Turcatti, Applicant argues that the reference does not, in fact, show unpredictability since the 20% DMSO used in the reference was present in a solution that also contains high salt, whereas the amended claims exclude such solutions (Remarks, page 10). As to Seo, Applicant argues that since neither the ethanol concentration nor washing in the presence of low salt is disclosed, the reference fails to demonstrate unpredictability for the currently claimed dissociation conditions (Remarks, page 10).
Response:
These arguments have been fully considered, but they were not persuasive.
Regarding Dambacher, Applicant is correct that the reference describes “alcohols (e.g., ethanol and isopropanol)” as fluids that stabilize a ternary complex, but the reference specifically includes the cognate nucleotide in this description. For example, in para. 79, Dambacher states, “As used herein, a ‘stabilizing fluid’ is a fluid that can contact a ternary complex without substantially promoting decomposition, dissolution, or loss of polymerase or nucleotide from the complex” (emphasis added). The remainder of para. 79 also discusses using a stabilizing fluid that does not allow components (polymerase or nucleotide) to partition into the stabilizing fluid. This clearly indicates that it is not predictable for organic solvent as broadly recited as in the amended claims to be capable of dissociating a cognate nucleotide from a ternary complex.
Regarding Turcatti, it is noted that the sequencing buffer of Turcatti does not always contain 500 mM NaCl. As can be seen on page 4, Turcatti also discloses a sequencing buffer that contains 250 mM NaCl, which is relatively close to the upper limit for salt in the claimed methods. Therefore, it is still reasonable to conclude that a buffer with, for example, 20% (v/v) DMSO and 200 mM NaCl may not be able to dissociate a cognate nucleotide from a ternary complex.
Regarding Seo, it is noted that the claimed dissociation conditions do not require salt to be present. Amended claim 17 recites “at most 200 mM salt,” which encompasses the use of no salt in the dissociation step. Therefore, it is still reasonable to conclude that Seo’s teachings are relevant to the claimed methods.
Argument:
Applicant additionally argues in this portion of the response that none of the references cited in the rejection discloses the claimed dissociation conditions (Remarks, page 10).
Response:
In response, it is noted that none of the cited references are alleged to teach the claimed dissociation conditions. Instead, the references are cited to illustrate the state of the prior art relative to the claimed invention.
Argument:
Applicant further argues that the specification and working examples provide sufficient guidance to enable practice of the full scope of the currently claimed methods without undue experimentation (Remarks, pages 10-11). Here, Applicant argues that nothing more than routine optimization would be required to practice the full scope of the claimed invention. Applicant also argues in this portion of the response that since “the dissociation targets the universal non-covalent binding forces of the nucleotide cognate rather than a specific property of the polymerase and/or template, the results obtained in the working examples are predictably transferrable across the genus of polymerases” (Remarks, page 11). Applicant further argues that paras. 41, 87, 88, and 124 of the specification as well as the experimental section provide sufficient guidance (Remarks, page 11).1
Response:
These arguments were not persuasive for the following reasons.
First, Applicant’s argument concerning targeting the binding affinity of the cognate nucleotide rather than the polymerase or template nucleic acid was unpersuasive for the reasons set forth above in response to Applicant’s arguments on pages 8-9 of the Remarks.
Second, it is not, in fact, clear that only routine experimentation would be required to enable the full scope of the claimed methods. The guidance in the specification, including the portions cited by Applicant, is either very general (see, e.g., paras. 87 and 88 cited by Applicant) or very narrow (see, e.g., pages 64-65 in the specification) and does not address, for example, how to apply the method to different template nucleic acids and/or different polymerases, nor is there any demonstration of the ability of the method to function, e.g., in the presence of a high concentration of organic solvent and no salt as encompassed by the claims. Then, since the teachings of Dambacher, Turcatti, Elias, and Nakano indicate that there is unpredictability associated with these aspects of the claimed methods, it is reasonable to conclude that more than routine experimentation would be required to enable the full scope of the claimed methods.
Lastly, it is noted that MPEP 2164.02 contradicts Applicant’s argument on page 10 of the Remarks that a claimed invention is enabled when the disclosure enables any mode of making and using the invention. More specifically, this section of the MPEP states that “Compliance with the enablement requirement…does not turn on whether an example is disclosed.” This section also notes that the presence of an example may not be sufficient if the results would not be expected to extend over the full scope of the claims. These teachings in the MPEP, and section 2164.02 as a whole, clearly indicate that a working example or enablement of some part of the claimed invention does not necessarily indicate that the entire claimed invention is enabled.
Since Applicant’s arguments were not persuasive, the rejection has been maintained with modifications to address the claim amendments and the cancellation of claims 18, 29, and 35.
Rejection of claims 17-42 under 35 U.S.C. 112(b)
Applicant argues that the rejection should be withdrawn (Remarks, pages 12-13). More specifically, Applicant argues that the rejection should be withdrawn in view of the amendments to the claims, especially claim 17 (Remarks, pages 12-13). Applicant also argues that claim 40 as written is, in fact, definite (Remarks, page 13). These arguments were persuasive. The rejection has been withdrawn.
Rejection of claims 36 and 37 under 35 U.S.C. 112(d)
Applicant argues that the rejection should be withdrawn in view of the amendments to claim 17, from which claims 36 and 37 depend (Remarks, pages 13-14).
This argument was persuasive. The rejection has been withdrawn.
Double Patenting
Applicant argues that the nonstatutory double patenting rejection citing US 11,421,262 should be withdrawn in view of the terminal disclaimer and associated fee filed with the response (Remarks, page 14).
This argument was not persuasive because a terminal disclaimer does not appear in the application file. The rejection has been maintained with modifications to address the claim amendments since it remains applicable.
Claim Objections
5. Claim 39 is objected to because its status identifier is incorrect.
Claim Rejections - 35 USC § 112
6. The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 17, 19-28, 30-34, and 36-42 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claims contain subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Factors to be considered in determining whether a disclosure meets the enablement requirement of 35 USC 112, first paragraph, have been described by the court in In re Wands, 8 USPQ2d 1400 (CA FC 1988). These factors include (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative
skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims. Each of these factors is discussed below.
Nature of the Invention
The instant claims are drawn to a sequencing method that comprises cycles of an examination step and a primer extension step carried out separately from one another. The examination step comprises detecting a ternary complex formed between a polymerase, a primed template nucleic acid, and nucleotide cognate comprising an exogenous label. The method also requires removal of the cognate nucleotide under chemical conditions that dissociate the nucleotide cognate from the ternary complex without causing removal of the polymerase.
The claimed invention is classified in the unpredictable arts of molecular biology and biochemistry.
Relative Skill of the Ordinary Artisan
The ordinary artisan typically holds a graduate degree and has at least several years of post-graduate laboratory and/or clinical experience.
Breadth of the Claims
The claims are rather broad in scope for at least the following reasons. First, they do not limit the polymerase or type of primed template in any way and encompass the use of DNA templates, RNA templates, hybrid templates, RNA-dependent RNA polymerases, DNA-dependent DNA polymerases, DNA-dependent RNA polymerases, and RNA-dependent DNA polymerases. Also, with the exception of claims 23-28 and 36, which limit the nucleotide cognate somewhat, the claims encompass the use of any type of nucleotide cognate (dNTP, rNTP, analogs) comprising any type of exogenous label. Further, the claims are broad with respect to the type of chemical conditions used to dissociate a nucleotide cognate from a ternary complex without causing removal of the polymerase. Independent claim 17 requires “at least 10% (v/v) organic solvent, and at most 200 mM salt.” This language encompasses any organic solvent, imposes no upper limit on the organic solvent concentration, and encompasses any salt or even no salt in the dissociation step. Claims 19-22 limit the solvent relative to claim 17, but they still broadly encompass many different types of chemical conditions for dissociation since they use broad terms like “an alcohol” or “a diol” and impose no further limitations on the organic solvent concentration or the type of salt. Thus, the amended claims are very broad in scope, encompassing a large and highly variable genus of template nucleic acids, polymerases, nucleotide cognates, and chemical conditions for dissociating a nucleotide cognate from a ternary complex.
State of the Prior Art
The prior art does describe sequencing-by-synthesis (SBS) and sequencing-by-binding (SBB) methods, but it does not teach or suggest the nucleotide cognate removal step set forth in step (ii) of independent claim 17. For example, Turcatti et al. (Nucleic Acids Research 2008; 36: e25; cited previously) and Seo et al. (Proceedings of the National Academy of Sciences, USA 2005; 102: 5926-5931; cited previously) each disclose an SBS method that comprises sequential incorporation of fluorescently labeled fluorescent nucleotides (see Turcatti at, e.g., the abstract and pages 2 and 4-5; see Seo at the abstract and pages 5927-5929 and Figure 4). Vijayan et al. (WO 2017/014762 A1; cited previously) discloses a SBB method (see, e.g., the abstract and paras. 2 and 25-31).
The art also contains negative teachings with respect to the claimed methods. For example, Dambacher et al. (US 2018/0208983 A1; cited previously) describes alcohols (e.g., ethanol and isopropanol) and some alcohol-containing solutions as “stabilizing fluids,” which “can contact a ternary complex without substantially promoting decomposition, dissolution, or loss of polymerase or nucleotide from the complex” (para. 79). See also paras. 215, 357, and 366 of Dambacher, which provides specific examples of solutions that are encompassed by the claims but do not appear to be capable of dissociating a nucleotide cognate from a ternary complex in the required manner.
As well, the teachings of each of Turcatti and Seo provide evidence that there is unpredictability associated with the claimed methods. In particular, Turcatti teaches use of a sequencing buffer containing 20% DMSO (v/v), but this sequencing buffer apparently does not result in dissociation of a nucleotide cognate from a ternary complex since different DMSO-containing buffers are used for washing (see pages 4-5). As well, Seo teaches the use of ethanol for washing between nucleotide incorporation steps, but the concentration of ethanol used is not reported, nor is it clear that the DNA polymerase is not removed during this wash step (pages 5928-5929, “SBS reaction on a Chip…” section as well as Fig. 4).
Taken together, these teachings in the art indicate that there is unpredictability as to whether a particular solution that meets the requirements of the claims will be capable of performing the required function of dissociating a nucleotide cognate from a ternary complex without also removing the polymerase. It is also reasonable to conclude that, given the aforementioned teachings in the art and also the breadth and variability of nucleic acid templates, polymerases, nucleotide cognates, and chemical conditions encompassed by the claims, there is likely to be a high degree of unpredictability as to the ability of any particular combination of template, polymerase, nucleotide cognate, and chemical conditions to perform the required function of dissociating a nucleotide cognate from a ternary complex without also removing the polymerase.
Guidance Presented in the Application & Working Examples
The guidance in the specification is limited compared to the breadth of the claims. As to nucleic acid templates, polymerases, and nucleotide cognates, the specification teaches that a wide variety of each may be used in the methods (see, e.g., page 17, lines 3-10 and page 17, lines 21 – page 18, line 5). The specification also provides guidance as to chemical conditions that may be useful for performing the required nucleotide cognate dissociation step (page 33, line 27 – page 34, line 30), but this guidance is quite broad, encompassing many different chemical conditions (i.e., different solvents and/or salts used at wide concentration ranges) as well as combinations of physical and chemical conditions.
The portion of the working example on pages 64-66 pertains to the claimed methods. Here, Applicant reports improved results when “lower salt washes” with NaCl were used (page 64, last para. – page 65, first full para.), but it is not clear that this example removed nucleotide cognates as required by the claims. Applicant also tested use of a “strip solution containing salt and ethanol” and observed improved results with this solution (pages 65-66). These conditions are much narrower than the instant claims since they are limited to a particular combination of salt and ethanol concentration as well as a particular combination of polymerase, nucleotide cognate, and primed template. It is not clear that Applicant’s results in the working example will extend over the full scope of the claims, particularly in view of the negative teachings in the art discussed above as well as the teachings in the art concerning unpredictability.
Quantity of Experimentation & Unpredictability
In view of the limitations in the specification and prior art, the ordinary artisan would have to conduct a very large quantity of highly unpredictable experimentation to practice the claimed methods. In particular, the ordinary artisan would have to determine which of the many different chemical conditions encompassed by the claims is capable of performing the required function of dissociating a nucleotide cognate from a ternary complex without also removing the polymerase. The ordinary artisan would have to perform this experimentation for each different combination of chemical conditions, nucleotide cognate type, primed template type, and polymerase, and it is not clear that the results obtained for one combination would extend to any other combination. The ordinary artisan would also have to conduct the required experimentation using not only very limited guidance provided by the specification and working example, but in spite of the negative teachings in the art cited above. Accordingly, the experimentation required would be inventive in nature and would have to be conducted with very little guidance and with no guarantee of success.
In view of the foregoing, claims 17, 19-28, 30-34, and 36-42 fail to comply with the enablement requirement.
Claim Rejections - 35 USC § 112(d)
7. The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 28 and 37 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 28 depends from claim 17 and recites “wherein the ternary complex of the examination step is stabilized by the presence of the reversibly terminated primer that precludes enzymatic incorporation of an incoming reversibly terminated nucleotide into the primer.” This recitation is not further limiting because it merely sets forth an inherent property of the reversibly terminated primer recited in claim 17. In other words, claim 28 does not require anything additional relative to claim 17. Accordingly, claim 28 is rejected as not further limiting.
Claim 37 depends from claim 17 and recites “wherein the repeating step reveals the sequence of the template nucleic acid.” This is not further limiting because it is already required by claim 17. More specifically, the requirement in the last two lines of claim 17 to perform multiple cycles of examination and primer extension would necessarily reveal the sequence of the template nucleic acid. Accordingly, claim 37 fails to add anything more to the method of claim 17, and it is rejected as not being further limiting.
Applicant may cancel the claims, amend the claims to place them in proper dependent form, or present a sufficient showing that the dependent claims comply with the statutory requirements.
Double Patenting
8. The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
9. Claims 17, 19, 20, 23, 26-28, 33, 34, and 36-39 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of U.S. Patent No. 11,421,262 B2.
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the ‘262 patent overlap in scope with the instant claims and recite or suggest all of their features.
The instant claims are drawn to a sequencing method comprising repeated cycles of an examination step and a primer extension step that are separate from one another.
Regarding the instant claim 17, claims 1, 4, and 8 of the ‘262 patent recite methods that, considered together, contain all of the limitations of the instant claim 17. More specifically, claim 1 of the ‘262 patent recites all of the required steps in the instant claim 17 except for the requirement for the use of chemical conditions to dissociate the nucleotide cognate and the requirement for a primer extension step. The nucleotide cognate dissociation step and primer extension step are recited in claims 4 and 8 of the ‘262 patent, respectively. Thus, the claims of the ‘262 patent suggest a method containing all of the limitations of the instant claim 17.
The limitations of the instant claims 19 and 20 are rendered obvious by claim 4 of the ‘262 patent. As discussed in MPEP 2144.05 I, overlapping ranges (e.g., as recited in claim 4 of the ‘262 patent and the instant claim 18) are prima facie obvious in the absence of unexpected results. In this case, no such evidence has been presented. And, further regarding the instant claims 19 and 20, ethanol as recited in claim 4 of the ‘262 patent is an alcohol and an organic solvent.
Regarding the instant claim 23, the claims of the ‘262 patent require the nucleotide cognate to contain an exogenous label (see, e.g., claim 1 of the ‘262 patent). The claims of the ‘262 patent do not specify that this label comprises a fluorophore, but this would have been obvious since fluorescently labeled nucleotides were routinely used in sequencing methods.
The additional limitations of the instant claims 26 and 27 are also suggested by the claims of the ‘262 patent. Each of these claims depends from the instant claim 17 and requires the use of reversibly terminated nucleotides in the examination step. The ordinary artisan would have recognized that any detectable nucleotide could be used in the examination step and accordingly would have selected reversibly terminated nucleotides as recited in the instant claims 26 and 27 with a reasonable expectation of success. The ordinary artisan also would have recognized that different reversibly terminated nucleotides could be added sequentially as recited in the instant claim 26 or in one step as recited in the instant claim 27, and accordingly, would have been motivated to select either order of adding reagents with a reasonable expectation of success. See also MPEP 2144.04 IV C, which notes that changing the order of mixing reagents is prima facie obvious in the absence of unexpected results. In this case, no evidence of unexpected results related to the instant claims 26 and 27 has been presented. Lastly, when opting to add nucleotides in a single step as recited in the instant claim 27, the ordinary artisan would have recognized that the exogenous label on the nucleotides would need to be different so that different nucleotide bases could be detected during the examination step. Thus, the instant claims 26 and 27 are not patentably distinct from the claims of the ‘262 patent.
Regarding the instant claim 28, as discussed below, the claim is not further limiting because it adds nothing in addition to the requirements of the instant claim 17. Therefore, claim 28 is also not patentably distinct from the claims of the ‘262 patent.
The additional limitations of the instant claims 33 and 34 are recited in claim 1 of the ‘262 patent. And, more specifically, regarding the instant claim 34, the polymerase is immobilized on the array recited in claim 1 of the ‘262 patent by way of its binding to the array-immobilized primed nucleic acid template.
The additional limitations of the instant claim 36 are also suggested by the claims of the ‘262 patent. This claim depends from the instant claim 17 and recites “wherein the reversibly terminated nucleotide does not comprise a label.” Not including a label on the reversibly terminated nucleotide added during the primer extension step would have been obvious to the ordinary artisan since the examination (i.e., label detection) step precedes the primer extension step. In other words, the ordinary artisan would have recognized that there is no need for a label on the reversibly terminated nucleotide incorporated during the primer extension step. Thus, the instant claim 36 is also not patentably distinct from the claims of the ‘262 patent.
Regarding the instant claim 37, as discussed below, the claim is not further limiting because it adds nothing in addition to the requirements of the instant claim 17. Therefore, claim 37 is also not patentably distinct from the claims of the ‘262 patent.
The additional limitations of the instant claims 38 and 39 are also suggested by the claims of the ‘262 patent. In particular, the claims of the ‘262 patent are directed to a method comprising multiple cycles of primer extension and examination. See, e.g., claims 1, 8, and 10 of the ‘262 patent. The ordinary artisan would have recognized that these steps could be repeated as many times as desired depending on the nucleic acid template to be sequenced.
Thus, the instant claims 17, 19, 20, 23, 26-28, 33, 34, and 36-39 are not patentably distinct from claims 1-10 of the ‘262 patent.
Conclusion
10. No claims are currently allowable. The claims have not been rejected with prior art due to their issues under 35 U.S.C. 112.
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 Angela Bertagna whose telephone number is (571)272-8291. The examiner can normally be reached 8-5, M-F.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Gary Benzion can be reached at 571-272-0782. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/ANGELA M. BERTAGNA/Primary Examiner, Art Unit 1681
1 These citations apparently correspond to the pre-grant publication of the instant application since the originally filed specification does not contain paragraph numbers.
Prosecution Insights