DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim 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.
Claim 3 recites the limitation "said support". There is insufficient antecedent basis for this limitation in the claim.
Double Patenting
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.
Claims 1-19 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No.11326203. Although the claims at issue are not identical, they are not patentably distinct from each other because they both claim similar methods for determining a sequence of a template nucleic acid molecule, comprising:
(a) generating a reaction mixture comprising said template nucleic acid molecule, a
primer capable of hybridizing to said template nucleic acid molecule, and a plurality of free nucleotide analogs, wherein a given free nucleotide analog of said plurality of free nucleotide analogs comprises a functional group (wherein said functional group comprises sulfur or selenium, or azido); (wherein said plurality of nucleotide analogs comprises a plurality of alpha-thio-deoxynucleotide triphosphates (α-S-dNTPs));
(b) subjecting said reaction mixture to conditions sufficient to conduct a primer extension reaction on said template nucleic acid molecule in presence of said primer, to incorporate said given free nucleotide analog comprising said functional group into a growing nucleic acid strand having sequence complementarity with said template nucleic acid molecule;
(c) upon incorporating said given free nucleotide analog into said growing nucleic acid
strand, reacting said functional group with a labeling reagent comprising a label to generate a labeled functional group (wherein said labeling reagent comprises a luminescent moiety, an optically-active moiety, a self-quenching dye, or a proximity quenching dye); (wherein (c) comprises a click reaction);
(d) detecting one or more signals indicative of said labeled functional group; and
(e) subjecting said labeled functional group to conditions sufficient to convert said labeled functional group to a moiety that is substantially unreactive with said labeling reagent (the patent discloses when said label is derived from said S-pyridyl-
containing reagent, (e) is conducted at a pH of about 5 to about 6) (see col.3 2nd para).
Claim Rejections - 35 USC § 102
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.
Claim(s) 1-4, 6-13 and 15 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Zhao et al. US 20100092957.
With regards to claim 1, Zhao discloses a method for determining a sequence of a template nucleic acid molecule (compositions and methods for nucleotide sequencing, Title; Cycles can be repeated to determine a sequence present in a template to which the primer is hybridized, Para. [0081]), comprising:
(a) providing a reaction mixture (reagent/sample admixtures, Para. [0146]) comprising said template nucleic acid molecule (The method can include the steps of incubating a template nucleic acid molecule, Para. [0082]), and a plurality of nucleotide analogs (methods generally utilize a DNA template, two primers, dNTPs and a DNA polymerase, Para. [0092]), wherein a nucleotide analog of said plurality of nucleotide analogs comprises a functional group (modified at the 3'-OH position of 2'-deoxynucleoside triphosphates, Para. [0027]);
(b) subjecting said reaction mixture to conditions sufficient to incorporate said nucleotide analog (incubating a nucleic acid molecule with a polymerase in the presence of a nucleoside triphosphate (NTP) comprising a label linked to the NTP by an enzymatically cleavable peptide linker, wherein a primer is extended to incorporate the NTP into a sequence complementary to the nucleic acid molecule, Para. [0074]; The method can include the steps of incubating a nucleic acid molecule with a polymerase, Para. [0078]; Wherein a primer is extended to incorporate the NTP into a sequence complementary to the nucleic acid molecule; and identifying the NTP in the complementary sequence, wherein identifying the NTP identifies at least a portion of the sequence of the nucleic acid molecule, Para. [0074]); (which is also viewed to be inclusive of instant claim 86).
(c) subsequent to (b) subjecting said growing nucleic acid strand and a labeling reagent comprising a label to conditions sufficient for functional group and said labeling reagent to react to provide a labeled functional group comprising said label (O-acetyl derivatives of ATP, CTP, and GTP follows the same general scheme, with additional steps to protect and deprotect the primary amino functions... If radiolabeled acetic anhydride is used, this serves to introduce a label into the ester blocking group, Para. [0054]; labels having reactive functional groups can be incorporated into a nucleic acid, nucleoside or nucleotide. The functional group can be subsequently covalently reacted with a primary label, Para. [0128]);
(d) detecting one or more signals indicative of said labeled functional group (by exposing the same reaction to multiple substrate-bound probes. For example dATP can be added to a probe-target hybrid, and the generation of a signal evaluated, Para. [0113]); (Each nucleotide base has a unique fluorescent color (dye) associated with it... detectable signal from the dye, Para. [0031]).
(e) subjecting said labeled functional group to conditions sufficient to convert said labeled functional group to a moiety that is substantially unreactive with said labeling reagent (there are many other potential reversible terminators which can be used in a primer extension method, Para. [0030]; O-acetyl derivatives of ATP, CTP, and GTP follows the same general scheme, with additional steps to protect and deprotect the primary amino functions... If radiolabeled acetic anhydride is used, this serves to introduce a label into the ester blocking group, Para. [0054]); (modified at the 3'-OH position of 2'-deoxynucleoside triphosphates, Para. [0027]); derivatives of the fluorophores exemplified herein can also be used, so long as they produce fluorescent signals having desired properties to suit a particular embodiment. If desired, a different fluorophore can be added to each of the four nucleotides such that the nucleotides can be used simultaneously and be independently detected, Para. [0185]).
Regarding Claim 2, Zhao discloses the method of claim 1, wherein said template nucleic acid molecule is immobilized to a support (A nucleic acid sample to be sequenced can be attached to a solid phase using methods and substrates described, Para. [0103]).
Regarding Claim 3, Zhao discloses the method of claim 1, wherein said support is a bead or a substantially planar surface (A printed microarray can contain 22.575 features on a surface having standard slide dimensions (about 1 inch by 3 inches), Para. [0157]).
Regarding Claim 4, Zhao discloses the method of claim 1, wherein said functional group comprises sulfur or selenium (Suitable functional groups include, but are not limited to... thiol, Para. [0128]).
Regarding Claim 6, Zhao discloses the method of claim 1, wherein the functional group comprises an azido group (Additional chemistries that are mild reactions that are performed in aqueous solution include azide plus alkyne and azide plus phosphine, Para. [0142]).
Regarding Claims 7-9, Zhao discloses the method of claim 1, wherein said labeling reagent comprises a luminescent moiety (electron-rich material Such as a metal; electrochemiluminescent label such as Ru(bpy)32+, Para. [0125]); wherein (c) comprises contacting said functional group with a solution comprising labeling reagent (As will be appreciated by those in the art, the configuration of an SBS method or SBE reaction can take on any of several forms. In particular embodiments, the reaction can be done in solution, and then the newly synthesized strands, with the base-specific detectable labels, can be detected. Para. [0112]).
Regarding Claims 10-11, Zhao discloses the method of claim 1 comprises contacting said functional group with a solution comprising said labeling reagent and wherein said solution comprises a derivative of said label, wherein said derivative lacks a detectable moiety of said label (Exemplary secondary labels are binding moieties. A binding moiety can be attached to a nucleic acid to allow detection or isolation of the nucleic acid via specific affinity for a receptor Para. ([0126]-[0127]).
Regarding Claim 12, Zhao discloses the method of claim 1, wherein (c) comprises covalently coupling said at least portion of said labeling reagent with at least a portion of said functional group (The functional group can be subsequently covalently reacted with a primary label, Para. [0128]).
Regarding Claim 13, Zhao discloses the method of claim 12, further comprising, subsequent to (c), subjecting said growing nucleic acid strand to one or more washing cycles (Binding partners that are specifically bound typically remain bound under the detection or separation conditions described herein, Para. [0126]).
Regarding Claim 15, Zhao discloses the method of claim 1, wherein said label is derived from Cy5 (and that different labels can be used such as Cy3, Cy5 or others set forth previously herein, Para. [0129]).
Claim Rejections - 35 USC § 103
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 5 is/are rejected under 35 U.S.C. 103 as being unpatentable over Zhao et al. US 20100092957 in view of Menchen et al. US 20160130644.
Zaho et al. is discussed above.
Regarding Claim 5, Zhao discloses the method of claim 4. Zhao fails to explicitly disclose wherein said plurality of nucleotide analogs comprises alpha-thio-deoxynucleotide triphosphates (α-S-dNTPs).
Menchen et al. is in the field of thiolated analogues for nucleic acid synthesis (Abstract) and teaches a plurality of free nucleotide analogs comprises alpha-thio-deoxynucleotide triphosphates (α-S-dNTPs) (the sulfur is bonded to the phosphate most proximate to the nucleoside, thus forming part of the α (alpha)-thiophosphate of the nucleoside polyphosphate, Para. [0030]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Zhao with the teaching of Menchen et al. for the purpose of increasing the efficiency of extension reactions as thiol bond formation increase net favorable free energy available to nucleotide incorporation (Menchen et al., Para. [0025]).
Claim(s) 14, 17-20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Zhao et al. US 20100092957 in further view of WO 2014/191981 Ramot At Tel-Aviv University Ltd. (hereinafter Ramot).
Zaho et al. is discussed above.
Regarding Claim 14, Zhao discloses the method of claim 1. Zhao fails to explicitly disclose wherein (c) comprises conducting an alkylation reaction using said label and said functional group.
Ramot is in the field of methodologies for labeling epigenetic modifications (Abstract) and teaches (c) comprises conducting an alkylation reaction using said label and said functional group (Chemical reactions that lead to a bond formation include... click reaction... alkylation reaction, Pg. 14, Lns. 20-24; the first and second reactive groups comprise (in no particular order) an azide and an alkyne. These two reactive groups may combine to form a triazole ring, as defined herein, as a linking moiety, Pg. 17, Lns. 16-20; the second reactive group or a chemical moiety comprising the second reactive group already forms a part in a labeling agent as a substituent, Pg. 17, Lns. 28-30).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Zhao with the teaching of Ramot for the purpose of single molecule level while maintaining high sensitivity (Ramot, Pg. 6, Lns. 24-26).
Regarding Claims 17-18, Zhao discloses the method of claim 1. Zhao fails to explicitly disclose wherein (c) comprises conducting a click reaction.
Ramot is in the field of methodologies for labeling epigenetic modifications (Abstract) and teaches c) comprises conducting a click reaction (The disclosed methodology is based on enzymatic glucosylation followed by a click chemistry reaction, and enables single molecule detection as well as global quantification of 5hmC in genomic DNA. (Ramot Pg. 6, Lns. 21-23 and pages 40-41).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Zhao with the teaching of Ramot for the purpose of single molecule level while maintaining high sensitivity (Ramot, Pg. 6, Lns. 24-26).
Regarding Claim 19, modified Zhao discloses the method of claim 17. Zhao fails to explicitly disclose wherein said click reaction is conducted without copper in the reaction.
Ramot teaches wherein a click reaction is conducted without copper in a reaction (The click chemistry reaction was performed, copper-free, Pg. 40, Lns. 18-19).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Zhao with the teaching of Ramot because copper can adversely affect a DNA sample (Ramot, Pg. 21, Lns. 21-23).
Regarding Claim 20, modified Zhao discloses the method of claim 17. Zhao fails to explicitly disclose wherein said click reaction is conducted in the presence of a reagent comprising dibenzocyclooctyne and azide moieties or trans-cycloocteyne and tetrazine moieties.
Ramot teaches a click reaction is conducted in the presence of a reagent comprising dibenzocyclooctyne and azide moieties (First, a copper-free reaction, with Alexa Fluor 647-DIBO (dibenzocyclooctyne) alkyne, Pg. 40, Ln. 26; cycloaddition of an alkyne to an azide moiety, Pg. 46, Ln. 30).
It would have been obvious to one of ordinary skill in the art at the time of the invention to modify Zhao with the teaching of Ramot for the purpose of single molecule level while maintaining high sensitivity (Ramot, Pg. 6, Lns. 24-26).
Claim 16 lacks an inventive step under PCT Article 33(3) as being obvious over Zhao et al. (hereinafter Zhao) in view of Krupey EP 0447133
Regarding Claim 16, modified Zhao discloses the method of claim 15. Zhao fails to explicitly disclose wherein said label is derived from said S-pyridyl-containing reagent, and wherein (e) is conducted at a pH of about 4 to about 6.
Krupey teaches a label derived from said S-pyridyl-containing reagent, and wherein (e) is conducted at a pH of about 4 to about 6 (reagent which contains one N-hydroxy succinimide ester moiety and one s-pyridyl disulfide moiety, Pg. 4, Ln. 41; the pH was lowered to 5.5, Pg .8, Ln. 35).
It would have been obvious to one of ordinary skill in the art at the time of the invention to modify Zhao with the teaching of Krupey for the purpose of increased amounts of optical label for sensitivity and enhanced levels of binding to target molecules. (Krupey, Pg. 2, Lns. 3-4).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JEZIA RILEY whose telephone number is (571)272-0786. The examiner can normally be reached 7:30-6:00pm.
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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.
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/JEZIA RILEY/ Primary Examiner, Art Unit 1681 31 August 2026
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