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 .
Election/Restrictions
2. Applicant's election with traverse of the following species for examination in the reply filed on June 23, 2026 is acknowledged: species A (test nucleotides that lack an exogenous fluorescent label).
The traversal is on the ground that it would not be unduly burdensome to examine both species together (Remarks, page 5). Applicant’s response also notes that the election is made with the understanding that rejoinder of non-elected species will occur when the generic invention is allowable (Remarks, page 5).
These arguments were persuasive. The election of species requirement has been withdrawn.
All of the pending claims are examined on the merits herein.
Priority
3. Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 120 and 35 U.S.C. 119(e) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
In this case, the disclosure of all of the prior-filed applications fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application.
More specifically, the prior-filed applications fail to provide support for the full scope of “performing consecutive first and second examination steps with reaction mixtures that comprise different concentrations of the at least one test nucleotide” as recited in step (b) of independent claim 65. This language encompasses the use of first and second reaction mixtures in which the concentration of the test nucleotide(s) is higher in the first reaction mixture compared to the second reaction mixture as well as the use of first and second reaction mixtures in which the concentration of the test nucleotide(s) is lower in the first reaction mixture compared to the second reaction mixture. The prior-filed applications, though, only provide support for “performing consecutive first and second examination steps with reaction mixtures in which the concentration of the test nucleotide(s) in first reaction mixture is lower compared to in the second reaction mixture.” See, e.g., pages 2-3 and 19-20 of the originally filed specification of prior-filed Application Serial No. 16/078,621. See also pages 10-11 of prior-filed Provisional Application Serial No. 62/326,356.
Then, since dependent claims 72 and 73 further limit the unsupported embodiment in claim 65 (i.e., the embodiment in which the concentration of the test nucleotide(s) is higher in the first reaction mixture compared to the second reaction mixture), they are also not supported by the prior-filed applications.
Further, as discussed below, claim 81 contains new matter. Accordingly, this claim is also not supported by the prior-filed applications.
Accordingly, the effective filing date of the instant claims 65-71, 74-79, 81, and 82 is July 28, 2023 when the concentration of the test nucleotide(s) in the first reaction mixture is higher compared to in the second reaction mixture. The effective filing date of claims 72 and 73 is also July 28, 2023 since those claims further limit the unsupported embodiment in claim 65. As well, the effective filing date of claim 81 is July 28, 2023 since that claim is not supported by the prior-filed applications.
When the concentration of the test nucleotide(s) in the first reaction mixture is lower compared to in the second reaction mixture, the effective filing date of claims 65-71, 74-79, and 82 is April 22, 2016.
Information Disclosure Statement
4. Applicant’s submission of an Information Disclosure Statement (IDS) on July 28, 2023 is acknowledged.
The foreign patent citations and non-patent literature citations 20-26, 29-30, 32-41, 43, and 44 have been lined through and not considered because the copy required by 37 CFR 1.98(a)(2) has not been provided either in the instant application or the prior-filed application identified in the transmittal letter accompanying the IDS.
Applicant is advised that the date of any re-submission of any item of information contained in this information disclosure statement 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).
Applicant is also reminded that any additional IDS filed in response to this Office action must comply with the provisions of 37 CFR 1.97(a) and 37 CFR 1.98(a)(4). As well, if necessary, payment of the appropriate size fee set forth in 37 CFR 1.17(v) is required with said additional IDS submission.
Drawings
5. The drawings filed on July 28, 2023 are acceptable.
Specification
6. The specification is objected to because the continuity information in the first paragraph should be updated to state that (i) prior-filed Application Serial No. 16/078,261 has issued as US 10,982,264, and (ii) prior-filed Application Serial No. 17/199,061 has been abandoned.
Claim Interpretation
7. The specification includes explicit definitions for several terms used in the claims and/or the specification. These definitions include the following:
(i) next correct nucleotide = cognate nucleotide = the nucleotide having a base complementary to the base of the next template nucleotide (page 14, lines 9-11);
(ii) test nucleotide = nucleotide being investigated for its ability to participate in formation of a ternary complex that further includes a primed template nucleic acid (or blocked primed template nucleic acid) and a polymerase (page 14, lines 29-31);
(iii) binary complex = a complex between a polymerase and a primed template nucleic acid (or blocked primed template nucleic acid), where the complex does not include a nucleotide (page 16, lines 13-15); and
(iv) ternary complex = a complex between a polymerase, a primed template nucleic acid (or blocked primed template nucleic acid), and the next correct nucleotide positioned immediately downstream of the primer and complementary to the template strand of the primed template nucleic acid or the blocked primed template nucleic acid (page 16, lines 16-20).
Claim Objections
8. Claim 71 is objected to because of the following minor informality. The term “polymerase” in line 1 should be replaced with “the DNA polymerase” to maintain consistency with claim 65.
Claims 72, 73, 76, and 77 are objected to because of the following minor informality. The term “the test nucleotide” in each claim should be replaced with “the at least one test nucleotide” or “the test nucleotide(s)” to better maintain consistency with claim 65.
Claim 77 is also objected to because the comma in line 2 is unnecessary.
Claim Rejections - 35 USC § 112
9. 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 65-79, 81, and 82 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 written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 65-79, 81, and 82 were first submitted in a preliminary amendment filed on April 15, 2024, which is after the filing date of the application. Thus, they are not part of the original disclosure. See MPEP 608.04(b) as well as MPEP 2163.06 III.
Claim 65
Independent claim 65 is drawn to a method for determining whether a test nucleotide is the next correct nucleotide in a sequencing method. Step (b) of the claim requires “performing consecutive first and second examination steps with reaction mixtures that comprise different concentrations of at least one test nucleotide.”
This language encompasses the use of first and second reaction mixtures in which the concentration of the test nucleotide(s) is higher in the first reaction mixture compared to the second reaction mixture as well as the use of first and second reaction mixtures in which the concentration of the test nucleotide(s) is lower in the first reaction mixture compared to the second reaction mixture.
Applicant’s remarks accompanying the preliminary amendment of April 15, 2024 point to the following portions of the original disclosure as providing support for the subject matter of claim 65: (i) original claim 1; (ii) page 31, lines 31-33; and (iii) page 56, line 33 – page 57, line 2. See page 6 of the Remarks filed on April 15, 2024.
The original disclosure, including the portions cited by Applicant, has been reviewed, but support was not found for the full scope of claim 65. As noted above, the claim language encompasses the use of first and second reaction mixtures in which the concentration of the test nucleotide(s) is higher in the first reaction mixture compared to the second reaction mixture as well as the use of first and second reaction mixtures in which the concentration of the test nucleotide(s) is lower in the first reaction mixture compared to the second reaction mixture. The original disclosure, though, only provides support for the use of first and second reaction mixtures in which the concentration of the test nucleotide(s) is lower in the first reaction mixture compared to the second reaction mixture (see, e.g., original claim 1 and page 19, line 25 – page 20, line 11 of the originally filed specification). The disclosure at page 31, lines 31-33 does not provide support for the aforementioned subject matter because it only describes the use of different nucleotides in consecutive reaction steps and does not support different concentrations of a test nucleotide in consecutive reaction steps as required by claim 65. The disclosure at page 56, line 33 – page 57, line 2 also does not provide support for the aforementioned subject matter because it does not disclose the use of different concentrations of a test nucleotide in consecutive reaction steps as required by claim 65.
Thus, claim 65 is rejected under 35 U.S.C. 112(a) for containing new matter.
Claims 66-71, 74-79, 81, and 82
Claims 66-71, 74-79, 81, and 82 depend, directly or indirectly, from claim 65. They are also rejected under 35 U.S.C. 112(a) because they do not correct the new matter issue in independent claim 65.
Claims 72 and 73
Claim 72 and 73 each depend from claim 65 and further limit the unsupported embodiment in claim 65 (i.e., the embodiment in which the concentration of the test nucleotide(s) is higher in the first reaction mixture compared to the second reaction mixture).
Applicant’s response filed on April 15, 2024 points to page 20, line 9 and page 20, line 10 of the originally filed specification, respectively, as providing support for the subject matter of claims 72 and 73.
The original disclosure, including the portions of page 20 of the originally filed specification, has been reviewed, but support was not found for the limitations of claims 72 and 73. Instead, the original disclosure only provides support for either omitting the test nucleotide in the first reaction mixture or providing a first reaction mixture in which the test nucleotide is present at a concentration that is 30% or more lower than the concentration of the test nucleotide in the second reaction mixture (see, e.g., page 20, lines 7-11).
Thus, claims 72 and 73 also contain new matter.
Claim 81
Claim 81 depends from claim 65 and recites “wherein the first reaction mixture comprises a nucleotide that is different from the test nucleotides.”
Applicant’s response filed on April 15, 2024 points to page 3, lines 2-3 and page 4, lines 17-19 as providing support for this subject matter.
The original disclosure, including the portion cited by Applicant has been reviewed, but support was not found for the subject matter of claim 81. The originally filed specification supports a first reaction mixture that is free of test nucleotides (page 3, lines 2-3 and page 4, lines 17-19) or a first reaction mixture that contains a test nucleotide (page 56, last para.), but it fails to provide support for a first reaction mixture that contains a nucleotide that is different from the test nucleotides as recited in claim 81. Accordingly, claim 81 also contains new matter.
Claim Rejections - 35 USC § 112
10. 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 65-79, 81, and 82 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 65 is indefinite because there is insufficient antecedent basis for “the labeled nucleotide molecule,” which is recited in the last line of the claim. The preceding portion of the claim makes no mention of a labeled nucleotide. As a result, it is not clear whether “the labeled nucleotide molecule” refers to the at least one test nucleotide recited in step (b), or if the claim requires one or both of the reaction mixtures in step (b) to contain a labeled nucleotide molecule in addition to the at least one test nucleotide.
Claims 66-79, 81, and 82 are also indefinite since they depend from claim 65 and do not correct its indefiniteness issues.
Claim 67 is also indefinite because there is insufficient antecedent basis for “the closed-complex,” which is recited in line 1. It appears that the claim was intended to depend from claim 66 rather than claim 65 since claim 66 provides antecedent basis for “the closed-complex.”
Claim 68 is also indefinite for an additional reason. This claim requires chemical incorporation of the test nucleotide into the primer of the primed template nucleic acid by formation of a phosphodiester bond, but it is not clear from the language in claims 65 and 68 that the chemical incorporation step occurs only when the test nucleotide is the “next correct nucleotide” as it seems should be the case. As a result, the requirements of claim 68 are not entirely clear, and the claim is rejected as indefinite.
Claim 81 is also indefinite for an additional reason. This claim depends from claim 65 and recites “wherein the first reaction mixture comprises a nucleotide that is different from the test nucleotides.” Claim 65, though, requires the first reaction mixture to contain “at least one test nucleotide.” It is unclear, therefore, whether claim 81 intends to require the first reaction mixture to contain more than one test nucleotide or if claim 81 contains a typographical error and intends to require the first reaction mixture to contain as few as one test nucleotide, consistent with claim 65.
Claim Rejections - 35 USC § 112
11. 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 76 and 82 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 76 depends from claim 65 and recites “wherein the test nucleotide does not comprise an exogenous fluorescent label.” As discussed above, claim 65 is indefinite because there is insufficient antecedent basis for “the labeled nucleotide molecule.” If “the labeled nucleotide molecule” in claim 65 refers to the test nucleotide, claim 76 does not comply with 35 U.S.C. 112(d) because it would no longer contain all of the elements of claim 65.
Claim 82 depends from claim 65 and recites “wherein the complex formed in step (a) is a binary complex.” This is not further limiting because a binary complex necessarily results from forming a complex between a DNA polymerase and primed template as recited in step (a) of claim 65. See also the definition for “binary complex” at page 16, lines 13-15.
Applicant may cancel the claim, amend the claim to be in proper dependent form, or present a sufficient showing that the dependent claim complies with the statutory requirements.
Claim Rejections - 35 USC § 102
12. 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.
13. Claims 65-69, 72, 73, 76-79, 81, and 82 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Vander Horn et al. (US 2010/0330570 A1; IDS reference).
The instant claims are drawn to a method for determining whether a test nucleotide is the next correct nucleotide in a sequencing method. The method comprises the following steps: (a) forming a complex between a DNA polymerase and a primed template nucleic acid, and (b) performing consecutive first and second examination steps using reaction mixtures that contain different concentrations of at least one test nucleotide, wherein the examination comprises determining whether the test nucleotide is the next correct nucleotide. The method further prohibits polymerase-mediated nucleotide incorporation into the primer in the primed template nucleic acid during the examination steps.
Vander Horn discloses nucleic acid sequencing methods that “rely on the fact that the polymerase transient-binding time for a complementary nucleotide is longer compared to that of a non-complementary nucleotide….[and] are conducted under any reaction condition that permits transient binding of a complementary or non-complementary nucleotide to a polymerase, and inhibits nucleotide incorporation” (abstract). See also paras. 10-16.
Regarding claims 65, 77, and 82, the sequencing methods of Vander Horn include the following steps (see, e.g., para. 10): (a) contacting at least one type of exogenously labeled nucleotide to an immobilized complex comprising a polymerase bound to a primed template nucleic acid (i.e., a binary complex) under conditions that permit transient binding, but not incorporation, of the labeled nucleotide to the polymerase-primed template complex; (b) exciting the exogenously labeled nucleotide with an excitation source; (c) detecting a signal, or change in a signal, from the transiently bound exogenously labeled nucleotide; and (d) identifying the transiently bound nucleotide. See also paras. 64-75, 113, 117, and 124-126 for additional description. As well, Examples 7 and 9 on pages 56-58 contain two examples of such a method.
Vander Horn further teaches that the “next correct” nucleotide can be distinguished from a “next incorrect” nucleotide by differences in the length, duration, or frequency of the transient binding between the nucleotide and the polymerase-primed template complex (see, e.g., paras. 64, 73, 113, and 121). Further regarding claim 65, Vander Horn also teaches that the polymerase used in the methods may be a DNA polymerase (paras. 71 & 96-99) in addition to teaching that the methods may comprise comparing binding measurements obtained for complexes formed between the primed template, the polymerase, and the next correct nucleotide (i.e., a complementary nucleotide) with measurements obtained for complexes formed between the primed template, the polymerase, and an incorrect next nucleotide (i.e., a non-complementary nucleotide) (see, e.g., paras. 64, 67, 73, and 113).
Lastly, further regarding claim 65 and also regarding claims 72 and 73, Vander Horn teaches that the method may include “performing consecutive first and second examination steps, using reaction mixtures that comprise different concentrations of at least one test nucleotide” (see, e.g., paras. 164 and 170, where reaction mixtures containing two different test nucleotides are used). The absence of the first test nucleotide in the second reaction mixture meets the requirements of claims 72 and 73.
Thus, Vander Horn anticipates the method of claims 65, 72, 73, 77, and 82.
Regarding claims 66 and 67, Vander Horn teaches that the method may include formation of a closed-complex (e.g., a stabilized ternary complex) during the examination step (see, e.g., paras. 71 and 92-95).
Regarding claim 68, Vander Horn teaches that the method may further include chemically incorporating the test nucleotide into the primer by formation of a phosphodiester bond (see, e.g., paras. 12, 71-72, 86-90, and 114).
Regarding claim 69, Vander Horn teaches that the method may include repeating steps (a)-(d) above (see, e.g., paras. 130-131, 170, 178-180, and 205).
Regarding claim 76, Vander Horn teaches that the test nucleotides need not contain an exogenous fluorescent label (see, e.g., paras. 259-262 and 264-269, where the use of labels other than fluorescent labels is taught).
Regarding claim 78, Vander Horn teaches that the DNA polymerase need not be labeled (paras. 124 and 174).
Regarding claim 79, Vander Horn teaches the use of wash steps to remove nucleotides in reaction mixtures that are not sequestered in a closed-complex (see, e.g., paras. 86, 126, 177, 205, and 581).
Regarding claim 81, when steps (a)-(d) above are repeated as taught by Vander Horn, the subsequent rounds of steps (a)-(d) use a first reaction mixture that contains a nucleotide that is different from the test nucleotides. This is because Vander Horn teaches that the incorporation step may be conducted using a reversible terminator nucleotide (paras. 165 and 168; see also paras. 114-115 and Example 9). The reaction mixture used for that incorporation step corresponds to the first reaction mixture in subsequent rounds of the method and thus includes a nucleotide that is different from the test nucleotide.
Claim Rejections - 35 USC § 103
14. 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.
15. Claims 70, 71, 74, and 75 are rejected under 35 U.S.C. 103 as being unpatentable over Vander Horn et al. (US 2010/0330570 A1; IDS reference).
As discussed above, the teachings of Vander Horn anticipate the methods of claims 65-69, 72, 73, 76-79, 81, and 82.
Regarding claim 70, Vander Horn teaches repeating the steps of the method to obtain sequence information for the template nucleic acid. The reference does not teach that the steps are repeated at least 50 times as required by claim 70, but this would have been prima facie obvious since the ordinary artisan would have had a general motivation to obtain as long of a sequencing read as possible, particularly for the longer targets of several hundred bases disclosed by Vander Horn in para. 385 and described as suitable for use in the disclosed method. Thus, the method of claim 70 is prima facie obvious over Vander Horn.
Regarding claim 71, Vander Horn does not explicitly state that the DNA polymerase is present at the same concentration in the first and second examination steps. This would have been prima facie obvious, though, to the ordinary artisan practicing the methods of Vander Horn. More specifically, the ordinary artisan seeking to measure transient binding events as disclosed in Vander Horn with the goal of determining which test nucleotide is the next correct base would have recognized that it would be optimal to keep the reaction conditions, which include the DNA polymerase concentration, the same for different examination steps with different test nucleotides to ensure that differences in transient binding times result from differences in the identity of the test nucleotide rather than the concentration of the DNA polymerase. Thus, the method of claim 71 is also prima facie obvious over Vander Horn.
Regarding claim 74, Vander Horn teaches performing successive reactions to measure and compare transient binding of different test nucleotides to determine which test nucleotide is the next correct nucleotide (see, e.g., paras. 164 and 170; see also paras. 67, 73, 113, and 178-180). The reference does not clearly teach that four examination steps are performed prior to an incorporation step as required by claim 74, but this would have been prima facie obvious to the ordinary artisan. More specifically, since (a) the method of Vander Horn aims to determine the nucleotide sequence of a target nucleic acid (para. 67), and (b) Vander Horn teaches performing transient binding measurements in the presence of a single type of test nucleotide (see, e.g., paras. 164 and 170), the ordinary artisan would have recognized that each position in the template nucleic acid could be analyzed by performing transient binding measurements using four separate reaction mixtures, each containing a different test nucleotide, in four separate examination steps and then comparing the results to determine which of the test nucleotides is the next correct nucleotide. The ordinary artisan would have had a reasonable expectation of success in view of the guidance throughout Vander Horn and also since the reference described performing transient binding measurements in the presence of a single type of test nucleotide (see, e.g., paras. 164 and 170). Thus, the method of claim 74 is prima facie obvious.
Regarding claim 75, Vander Horn teaches that the reaction mixtures used in the examination steps may contain more than one test nucleotide (see, e.g., para. 171). This in combination with the fact the method of Vander Horn is designed to determine the sequence of a nucleic acid template (para. 67) would have suggested to the ordinary artisan that different reaction mixtures could contain four different test nucleotides to account for all possibilities at each position in the template nucleic acid. Vander Horn does not suggest altering the concentration of the test nucleotides between reaction mixtures as required since claim 75 depends from claim 65, but as discussed in MPEP 2144.05 II, differences in known results-effective variables, such as concentrations, are prima facie obvious in the absence of unexpected results. In this case, no evidence of unexpected results with respect to the required concentration difference has been presented. Thus, the method of claim 75 is prima facie obvious.
Double Patenting
16. 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.
17. Claims 65-71, 74, 76-79, 81, and 82 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 10,982,264 B2 (IDS reference).
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the ‘264 patent overlap in scope with the instant claims and teach or suggest all of their limitations.
The instant claims are drawn to a method for determining whether a test nucleotide is the next correct nucleotide in a sequencing method. The method comprises the following steps: (a) forming a complex between a DNA polymerase and a primed template nucleic acid, and (b) performing consecutive first and second examination steps using reaction mixtures that contain different concentrations of at least one test nucleotide. The method further precludes polymerase-mediated nucleotide incorporation into the primer in the primed template nucleic acid during the examination steps.
The claims of the ‘264 patent are also drawn to a method for determining whether a test nucleotide is the next correct nucleotide in a sequencing method. Like the instant claims, the claims of the ‘264 patent comprise the following steps: (a) forming a complex between a DNA polymerase and a primed template nucleic acid, and (b) performing consecutive first and second examination steps using reaction mixtures that contain different concentrations of at least one test nucleotide, wherein the examination steps do not include polymerase-mediated nucleotide incorporation into the primer in the primed template nucleic acid. See claim 1 of the ‘264 application.
Regarding the instant claim 65, claim 1 of the ‘264 patent recites all of its method steps as well as additional elements (e.g., the use of more than two reaction mixtures and corresponding examination steps). See claim 1 of the ‘264 patent. Thus, claim 1 of the ‘264 patent recites a species of the method more generically recited in the instant claim 65. As noted in MPEP 804, a species claim anticipates a more generic claim. Thus, the instant claim 65 is not patentably distinct from claim 1 of the ‘264 patent.
Regarding the instant claims 66 and 67, claim 1 of the ‘264 patent states that a ternary complex is formed. It is not clear that this ternary complex is a stabilized ternary complex, but this would have been an obvious modification. More specifically, the ordinary artisan would have recognized that formation of a stabilized ternary complex would facilitate the required analysis of binding between the test nucleotide and the DNA polymerase and primed template in the complex by ensuring that the complex is stable enough for analysis. the ordinary artisan would have had a reasonable expectation of success since methods for stabilizing a ternary complex were well-known in the art prior to the effective filing date of the claimed invention. Thus, the instant claims 66 and 67 are not patentably distinct from the claims of the ‘264 patent.
The limitations of the instant claim 68 are recited in claim 4 of the ‘264 patent.
The limitations of the instant claims 69 and 70 are recited in claims 5 and 9 of the ‘264 patent.
Regarding the instant claim 71, the claims of the ‘264 application do not state that the DNA polymerase is present at the same concentration in the first and second examination steps. This would have been prima facie obvious, though, to the ordinary artisan practicing the methods recited in the claims of the ‘264 patent. More specifically, the ordinary artisan seeking to measure transient binding events as disclosed in the claims of the ‘264 patent with the goal of determining which test nucleotide is the next correct base would have recognized that it would be optimal to keep the reaction conditions, which include the DNA polymerase concentration, the same for different examination steps with different test nucleotides to ensure that differences in transient binding times result from differences in the identity of the test nucleotide rather than the concentration of the DNA polymerase. Thus, the instant claim 74 is not patentably distinct from the claims of the ‘264 patent.
Regarding the instant claim 74, claim 1 of the ‘264 patent discloses performing successive reactions to measure and compare transient binding of different test nucleotides to determine which test nucleotide is the next correct nucleotide. The claims of the ‘264 patent do not teach that four examination steps are performed prior to an incorporation step as required by the instant claim 74, but this would have been prima facie obvious to the ordinary artisan. More specifically, since (a) the method recited in the claims of the ‘264 patent aims to determine the nucleotide sequence of a target nucleic acid, and (b) claim 1 of the ‘264 patent recites performing transient binding measurements in the presence of a single type of test nucleotide, the ordinary artisan would have recognized that each position in the template nucleic acid could be analyzed by performing transient binding measurements using four separate reaction mixtures, each containing a different test nucleotide, in four separate examination steps and then comparing the results to determine which of the test nucleotides is the next correct nucleotide. The ordinary artisan would have had a reasonable expectation of success in view of the guidance throughout the claims of the ‘264 patent and also since the reference described performing transient binding measurements in the presence of a single type of test nucleotide in claim 1. Thus, the instant claim 74 is not patentably distinct from the claims of the ‘264 patent.
The limitations of the instant claims 76-78 are recited in claims 12-14, respectively, of the ‘264 patent.
Regarding the instant claim 79, the claims of the ‘264 patent do not recite use of a wash step to remove test nucleotides not sequestered in a closed-complex. This would have been an obvious modification, though, because the ordinary artisan would have recognized that washing nucleotides not in the closed-complex would eliminate the detection of signals from nucleotides other than nucleotides in the closed-complex. Thus, the instant claim 79 is not patentably distinct from the claims of the ‘264 patent.
The limitations of the instant claims 81 and 82 are recited in claims 17 and 18, respectively, of the ‘264 patent.
Conclusion
18. No claims are currently allowable.
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
Prosecution Insights