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
Applicant's election with traverse of Group I, in claim 10: second nucleotide mixture comprises: (2) an irreversible blocking nucleotide; In claim 11: (1) the first nucleotide mixture comprises a nucleotide selected from the group consisting of: an unlabeled first nucleotide, an unlabeled second nucleotide, an unlabeled third nucleotide, an unlabeled fourth nucleotide, or any combination thereof; In claim 12: (2) wherein in step (c), the extension is an extension of one nucleotide; In claim 13: (3) the ratio of the first nucleotide labeled with the first label to the unlabeled first nucleotide is 20:1, 1:10, 1:1 or 3:2; In claim 14: the second nucleotide mixture comprises: (3) an unlabeled first nucleotide, an unlabeled second nucleotide, an unlabeled third nucleotide, an unlabeled fourth nucleotide, and a first irreversible blocking nucleotide, a second irreversible blocking nucleotide, a third irreversible blocking nucleotide, and a fourth irreversible blocking nucleotide; In claim 15: (1) the ratio of the unlabeled first nucleotide to the first irreversible blocking nucleotide is 100:1 to 1:100; In claim 16: (1) the first label, the second label, the third label and the fourth label are each independently the same or different; In claim 17: (5) when the first nucleotide mixture comprises a first nucleotide labeled. In the reply filed on 7/1/2026 is acknowledged. The traversal is on the ground(s) that,” Applicant respectfully submits that there would not be a serious burden on the Examiner if all the species of the pending claims were searched together. The nature of the claims, and the subject matter encompassed by the claims, is such that there would be no undue burden on the Examiner to consider all the claims at the same time”.. This is not found persuasive because searching the kit will not inherently provide are on the method as detailed in the restriction requirement. Further searching one species encompassed by the dependent claims will not inherently provide art on the other species of the claims, unless applicant is willing on the record to indicate they are all obvious variants.
Claims 18-28 withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 7/1/2026.
Priority
The instant application was filed 03/04/2024 and is a national stage entry of PCT/CN2021/116930 with an international filing date: 09/07/2021.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 4/15/2024 and 11/10/2025 are being considered by the examiner.
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 10-17 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 10 is indefinite because it lacks a positive active step relating back to the preamble. The preamble recites a method or analyzing a sequence of target polynucleotide, however the last positive active step is drawn to repeating steps (c) to (g) one or more time. Therefore it is unclear as to whether the method is drawn to analyzing a sequence of target polynucleotide or repeating steps (c) to (g) one or more time. Further the claim recites, “e) not performing this step if at least one nucleotide in the second nucleotide mixture comprises an irreversible blocking nucleotide; contacting the product of the previous step with a polymerase and a third nucleotide mixture under a condition that allows the polymerase to perform a nucleotide polymerization reaction such that the growing chain is extended if the second nucleotide mixture does not comprise an irreversible blocking nucleotide; wherein the third nucleotide mixture comprises at least one irreversible blocking nucleotide.” Thus the claim is confusing and unclear what is required or encompassed or is not being performed.
Claim 10 recites, “protecting group capable of reversibly blocking nucleic acid chain extension.” The recitation suggests there are, “protecting group incapable of reversibly blocking nucleic acid chain extension.” The specification and claims provide no standard and definition of how to differentiate protecting group capable of reversibly blocking nucleic acid chain extension from protecting group incapable of reversibly blocking nucleic acid chain extension.
Claim 10 further recites, “(f) detecting the presence of a label in the product of the previous step.” The presence and the previous step lack antecedent basis as they are not previously recited in the claim. Further the recitation of “the previous step” is confusing as step (e) recites, “not performing this step.” Thus the metes and bounds are unclear.
Applicant elected a species from claim 12 of “ (2) wherein in step (c), the extension is an extension of one nucleotide.” Applicant elected species for claim 13 which depends from claim 12, “(3) the ratio of the first nucleotide labeled with the first label to the unlabeled first nucleotide is 20:1, 1:10, 1:1 or 3:2.” Thus the metes and bounds are unclear in view of the election. “The ratio,” “the first label,” “the unlabeled” lacks antecedent basis in the elected species. Thus the claim is confusing and unclear.
Claim 15 recites, “(1) the ratio of the unlabeled first nucleotide to the first irreversible blocking nucleotide is 100:1 to 1:100.” The metes and bounds are unclear as claim 14 and 10 from which claim 15 do not recite “the ratio” Thus the metes and bounds are unclear what ratio the claim is referencing.
Claim 16 recites, “AlexaFluor, Bodipy, CyS, Cy3, , Texas Red. These are trademarks or tradenames. MPEP 2173.05 (u) states, “trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of the 35 U.S.C. 112, second paragraph. Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. In fact, the value of a trademark would be lost to the extent that it became descriptive of a product, rather than used as an identification of a source or origin of a product. Thus, the use of a trademark or trade name in a claim to identify or describe a material or product would not only render a claim indefinite, but would also constitute an improper use of the trademark or trade name.”
Claim 16 further recites, “1) the first label, the second label, the third label and the fourth label are each independently the same or different; (2) the first label, the second label, the third label and the fourth label are different; (3) the first label, the second label, the third label and the fourth label are luminescent labels; (4) the first label, the second label, the third label and the fourth label are each independently selected from the group consisting of coumarin, AlexaFluor, Bodipy, fluorescein, tetramethylrhodamine, phenoxazine, acridine, CyS, Cy3, AF532, Texas Red and derivative thereof;”….” (8) the first nucleotide, the second nucleotide, the third nucleotide and the fourth nucleotide are each independently selected from the group consisting of A, T, C, G, U; (9) the first nucleotide, the second nucleotide, the third nucleotide and the fourth nucleotide are different; (10) the first nucleotide, the second nucleotide, the third nucleotide and the fourth nucleotide are A, T, C, G, respectively; (11) the first irreversible blocking nucleotide, the second irreversible blocking nucleotide, the third irreversible blocking nucleotide and the fourth irreversible blocking nucleotide are each independently selected from the group consisting of A, T, C, G, U; (12) the first irreversible blocking nucleotide, the second irreversible blocking nucleotide, the third irreversible blocking nucleotide and the fourth irreversible blocking nucleotide are different; and, (13) the first irreversible blocking nucleotide, the second irreversible blocking nucleotide, the third irreversible blocking nucleotide and the fourth irreversible blocking nucleotide are A, T, C, G, respectively. “ All the recitations with definite articles lack antecedent basis as neither claim 16 nor claim 10 provide antecedent basis for the limitations.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim(s) 10-17 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ju (WO02/29003) and Gordon (US20130137091).
With regards to claim 10, Ju is considered to represent the most relevant state of the art and discloses a method for sequencing a nucleic acid by detecting the identity of a nucleotide analogue after the nucleotide analogue is incorporated into a growing strand of DNA in a polymerase reaction, which comprises the following steps: (i) attaching a 5'end of the nucleic acid to a solid surface; (ii) attaching a primer to the nucleic acid attached to the solid surface; (iii) adding a polymerase and one or more different nucleotide analogues to the nucleic acid to thereby incorporate a nucleotide analogue into the growing strand of DNA, wherein the incorporated nucleotide analogue terminates the polymerase reaction and wherein each different nucleotide analogue comprises (a) a base selected from the group consisting of adenine, guanine, cytosine, thymine, and uracil, and their analogues; (b) a unique label attached through a cleavable linker to the base or to an analogue of the base; (c) a deoxyribose; and (d) a cleavable chemical group to cap an-OH group at a 3'-position of the deoxyribose ; (iv) washing the solid surface to remove unincorporated nucleotide analogues; (v) detecting the unique label attached to the nucleotide analogue that has been incorporated into the growing strand of DNA, so as to thereby identify the incorporated nucleotide analogue; (vi) adding one or more chemical compounds to permanently cap any unreacted-OH group on the primer attached to the nucleic acid or on a primer extension strand formed by adding one or more nucleotides or nucleotide analogues to the primer; (vii) cleaving the cleavable linker between the nucleotide analogue that was incorporated into the growing strand of DNA and the unique label; (viii) cleaving the cleavable chemical capping the-OH group at the 3'-position of the deoxyribose to uncap the-OH group, and washing the solid surface to remove cleaved compounds; and (ix) repeating steps (iii) through (viii) so as to detect the identity of a newly incorporated nucleotide analogue into the growing strand of DNA (cl. 1 ); wherein the chemical compounds added in step (vi) to permanently cap any unreacted OH group on the primer attached to the nucleic acid or on the primer extension strand are a polymerase and one or more different dideoxynucleotides or analogues of dideoxynucleotides (cl. 23).
The only difference between JU and the instant claim is step the order of steps of the claims.
The courts have haled that rearrangement of steps is obvious in the absence of unexpected results. Ex parte Rubin, 128 USPQ 440 (Bd. App. 1959) (Prior art reference disclosing a process of making a laminated sheet wherein a base sheet is first coated with a metallic film and thereafter impregnated with a thermosetting material was held to render prima facie obvious claims directed to a process of making a laminated sheet by reversing the order of the prior art process steps.). See also In re Burhans, 154 F.2d 690, 69 USPQ 330 (CCPA 1946) (selection of any order of performing process steps is prima facie obvious in the absence of new or unexpected results); In re Gibson, 39 F.2d 975, 5 USPQ 230 (CCPA 1930) (Selection of any order of mixing ingredients is prima facie obvious.).
Ju does not specifically teach the use of unlabeled nucleotides.
However, Gordon teaches, “[0152] he present invention contemplates a number of ways to minimize or eliminate this undesirable effect, including but not limited to: a) reducing the amount of labeled nucleotides incorporated in the template; b) reducing the size of the spacer arm or eliminate it completely by carefully designing nucleotide analogs; and c) change the reactivity of the spacer arm groups or their charge by performing a chemical "capping" step, where specific reagent is added to react only with groups on the spacer arm. [0153] Reducing the amount of labeled nucleotides that are incorporated can be accomplished by reducing the concentration of labeled nucleotides in the extension solution, and/or by mixing labeled nucleotides (reversible terminators) with non-labeled reversibly terminating nucleotides (e.g. where the non-labeled nucleotides are employed in ratios between 1:1 and 1000:1 relative to the labeled nucleotides, but more preferably in ratios between 10:1 and 100:1).”
Therefore it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claim to provide unlabeled nucleotides with the labeled nucleotides. The artisan would be motivated as Gordon teaches this minimizes or eliminates undesirable effects. The artisan would have a reasonable expectation of success as Gordon teaches it was known.
With regards to claim 12, Ju and Gordon both teach the use of reversibly and irreversibly blocked nucleotide analogues.
Therefore it would have been prima facie obvious to one of ordinary skill in the art the addition of a blocked nucleotide analogue (reversible or irreversible) would result in a single nucleotide be added to the primer. The artisan would be motivated to use reversibly or irreversibly nucleotide analogues to limit the incorporation of a single nucleotide at time to allow for the determination of the sequence and/or detection of a SNP. The artisan would have a reasonable expectation of success as the artisan is merely using known reagents in known methods.
Claim 13 is unclear in view of the election of claim 12.
However to promoter compact prosecution, Gordon teaches , “[0152] he present invention contemplates a number of ways to minimize or eliminate this undesirable effect, including but not limited to: a) reducing the amount of labeled nucleotides incorporated in the template; b) reducing the size of the spacer arm or eliminate it completely by carefully designing nucleotide analogs; and c) change the reactivity of the spacer arm groups or their charge by performing a chemical "capping" step, where specific reagent is added to react only with groups on the spacer arm. [0153] Reducing the amount of labeled nucleotides that are incorporated can be accomplished by reducing the concentration of labeled nucleotides in the extension solution, and/or by mixing labeled nucleotides (reversible terminators) with non-labeled reversibly terminating nucleotides (e.g. where the non-labeled nucleotides are employed in ratios between 1:1 and 1000:1 relative to the labeled nucleotides, but more preferably in ratios between 10:1 and 100:1).”
Therefore it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claim to provide unlabeled nucleotides with the labeled nucleotides at a ratio between 1:1 and 1000:1. The artisan would be motivated as Gordon teaches this minimizes or eliminates undesirable effects. The artisan would have a reasonable expectation of success as Gordon teaches it was known.
With regards to claim 14, Gordon teaches , “[0152] he present invention contemplates a number of ways to minimize or eliminate this undesirable effect, including but not limited to: a) reducing the amount of labeled nucleotides incorporated in the template; b) reducing the size of the spacer arm or eliminate it completely by carefully designing nucleotide analogs; and c) change the reactivity of the spacer arm groups or their charge by performing a chemical "capping" step, where specific reagent is added to react only with groups on the spacer arm. [0153] Reducing the amount of labeled nucleotides that are incorporated can be accomplished by reducing the concentration of labeled nucleotides in the extension solution, and/or by mixing labeled nucleotides (reversible terminators) with non-labeled reversibly terminating nucleotides (e.g. where the non-labeled nucleotides are employed in ratios between 1:1 and 1000:1 relative to the labeled nucleotides, but more preferably in ratios between 10:1 and 100:1).”
Therefore it would have been prima facie obvious to one of ordinary skill in the art the addition of a blocked unlabeled nucleotide analogues (irreversible) for all 4 bases with a small portion of a labeled blocked nucleotide analogue would result in a single nucleotide be added to the primer. The artisan would be motivated to use irreversibly nucleotide analogues to limit the incorporation of a single nucleotide at time to allow for the determination of the sequence and/or detection of a SNP. The artisan would be motivated to use labeled and unlabeled nucleotides as Gordon teaches this minimizes or eliminates undesirable effects. The artisan would have a reasonable expectation of success as the artisan is merely using known reagents in known methods.
With regards to claim 15, Gordon teaches , “[0152] he present invention contemplates a number of ways to minimize or eliminate this undesirable effect, including but not limited to: a) reducing the amount of labeled nucleotides incorporated in the template; b) reducing the size of the spacer arm or eliminate it completely by carefully designing nucleotide analogs; and c) change the reactivity of the spacer arm groups or their charge by performing a chemical "capping" step, where specific reagent is added to react only with groups on the spacer arm. [0153] Reducing the amount of labeled nucleotides that are incorporated can be accomplished by reducing the concentration of labeled nucleotides in the extension solution, and/or by mixing labeled nucleotides (reversible terminators) with non-labeled reversibly terminating nucleotides (e.g. where the non-labeled nucleotides are employed in ratios between 1:1 and 1000:1 relative to the labeled nucleotides, but more preferably in ratios between 10:1 and 100:1).”
Therefore it would have been prima facie obvious to one of ordinary skill in the art the addition of a blocked unlabeled nucleotide analogues (irreversible) for all 4 bases with a small portion of a labeled irreversible blocked nucleotide analogue would result in a single nucleotide be added to the primer. The artisan would be motivated to use irreversibly nucleotide analogues to limit the incorporation of a single nucleotide at time to allow for the determination of the sequence and/or detection of a SNP. The artisan would be motivated to use labeled and unlabeled nucleotides as Gordon teaches this minimizes or eliminates undesirable effects. The artisan would have a reasonable expectation of success as the artisan is merely using known reagents in known methods.
With regards to claim 16, Ju and Gordon teach each nucleotide analogue can have a unique label.
With regards to claim 17. Ju and Gordon teach fluorescent labels.
Summary
No claims are allowed.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to STEVEN C POHNERT PhD whose telephone number is (571)272-3803. The examiner can normally be reached Monday- Friday about 6:00 AM-5:00 PM, every second Friday off.
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/Steven Pohnert/Primary Examiner, Art Unit 1683
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