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 .
Detailed Action
This office action is a response to applicant’s communication submitted February 9, 2026, wherein claims 1, 2, 4, 13, 16, and 25 are amended. This application is a continuation of PCT/IB2020/059298, filed October 2, 2020, which claims benefit of foreign application GB1914282.7, filed October 3, 2019.
Claims 1-25 are pending in this application.
Priority
This action claims priority to foreign application GB1914282.7. However, a certified copy of the foreign priority document has not been received.
Election/Restrictions
Applicant’s provisional election with traverse of group I, claims 1-23, drawn to a method of synthesizing a polynucleotide, filed December 9, 2025, is acknowledged. Applicant’s arguments of record with respect to the aforementioned traversal are acknowledged and found to be not persuasive to remove the requirement for restriction. Specifically, Applicant argues that 35 USC 121 states that restriction is only permissible between inventions that are both independent and distinct. However, this is not the manner in which this statute is to be interpreted. A discussion of the proper interpretation of this statute in MPEP 802.01 concludes that, “The law has long been established that dependent inventions (frequently termed related inventions) such as used for illustration above may be properly divided if they are, in fact, "distinct" inventions, even though dependent.” Therefore groups II defines subject matter that is related to but distinct from the subject matter of group I, in this case for example a product produced by the process of group I.
Applicant further argues that the office has not shown a serious burden for examining both species together. However, In the present case it is notes that claim 24 is simply directed to a nucleic acid. Since the structure of a nucleic acid is independent of the method used to synthesize it, and because nothing about the process of claim 1 requires a specific structure of any of the nucleic acids, claim 24 could potentially be infringed by a wider variety of nucleic acids of varying arbitrary sequence, requiring a much broader search than the method of claim 1 directed to a set of specific synthetic transformations. Furthermore because all of the structural features of the nucleic acids included in the kit of claim 25 are functionally defined, once again, this kit could potentially be infringed by a wide variety of arbitrary collections of nucleic acids whose structure could be interpreted as potentially meeting the claimed functional limitations. Thus the prior art search necessitated by this group would be fundamentally different from the one required for group I, necessitating an undue search burden to examine them both together.
The election of nucleoside strand (i), spacer C18, FAM fluorophore, and glycosylase enzyme, is acknowledged.
Claims 24 and 25 are 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. Election was made with traverse in the reply filed on February 9, 2026.
Claims 1-23 are pending in this application and examined on the merits herein.
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 2-4 and 6 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 2, which depends from claim 1, refers to further definition of the 3’ and 5’ blockers. However, the base claim 1 includes reference to multiple 3’- and ‘- blocking groups in various different polynucleotide species. It is unclear whether the definition in claim 2 refers to all of the blocking groups in all of the polynucleotide species, or only to one specific blocking group, r3endering clai m2 and its dependent claims indefinite.
Claim 3 describes spacers C3, C6, C9, C12, and C18. It is unclear form the claims and specification what structure these spacers are intended to have. Furthermore the prior art does not provide a sufficiently universally agreed upon definition of these terms to render them definite without further explanation.
Claim 4 contains the trademark/trade name Alexa Fluor®. Claim 6 contains the trade name dynabeads®. Where a 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 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See 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. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe a fluorescent label and a magnetic solid support bead, and, accordingly, the identification/description is indefinite.
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.
Claims 1, 2, 7, 9, and 10 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Jacobson et al. (PCT international publication WO2011/150168, Reference included with PTO-1449)
Independent claim 1 is directed to a method of synthesizing a single or double stranded polynucleotide comprising steps of providing a blocked starter strand, digesting the strand or strands with a glycosylase to truncate it, ligating a further blocked segment comprising an additional nucleotide to the strand, and repeating the process until the desired polynucleotide has been constructed. The starter and ligation strands are described functionally, as containing regions described as “segment 1,” “segment 2,” “segment 3,” “additional nucleotide,” ‘CUCM1,” and “CUCM2.” In the case of “segment 1,” “segment 2,” “segment 3,” “additional nucleotide,” there is no limitation as to the specific nucleotide sequence of these segments, so any sequence could infringe them. In the case of “CUCM1” and “CUCM2” the only structural requirement is that they are cleaved in the presence of the glycosylase.
Jacobson et al. discloses a method of synthesizing a nucleic acid having a predefined sequence on a solid support. (p. 2 paragraph 5) This process comprises steps of providing a support comprising an anchor oligonucleotide attached to the support by the 3’- end and having a free 5’- end, hybridizing a partially double stranded oligonucleotide to the anchor to produce a 5’- overhang, ligating said oligonucleotide to the anchor, removing unwanted nucleotides from the ligated product, and repeating the steps to add additional nucleotides. (p. 2 paragraph 6) Repeatedly performing this process would involve performing the same steps recited in present claim 1. Regarding the identity of the enzyme used to remove the excess nucleotides, in one embodiment this is a DNA uracil glycosylase, or UDG. (p. 20 paragraph 44) This process is pictured in figure 7:
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1
Regarding the specific structures of the polynucleotides pictured herein, the “s” and “p” nucleotides are reasonably considered to make up segments 1-3 in the claimed structures and the uracil nucleotides are reasonably considered to make up the “CUCM” motifs. Still further, Jacobson et al. describes the use of fluorophores attached to the ends of the polynucleotdies, which would serve as blockers as recited in present claim 1. (p. 21 paragraph 48 – p. 22 paragraph 50)
Regarding claim 2, as discussed above, the blocking group is a fluorophore. Regarding claims 7, 9, and 10, the glycosylase cleavage motif comprises a uracil which corresponds to nucleobase “Z”. This would include embodiments of claims 7 and 9 wherein x and z are 0. Regarding claim 10, any number of flanking nucleobases could be interpreted as being part of the “N” bases in the motif of claim 10.
Therefore Jacobson et al. anticipates the present claims.
Claims 1, 5-7, 9, 10, 22, and 23 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Milton et al. (PCT international publication WO2018/134616, Reference included with PTO-1449)
Independent claim 1 is directed to a method of synthesizing a single or double stranded polynucleotide comprising steps of providing a blocked starter strand, digesting the strand or strands with a glycosylase to truncate it, ligating a further blocked segment comprising an additional nucleotide to the strand, and repeating the process until the desired polynucleotide has been constructed. The starter and ligation strands are described functionally, as containing regions described as “segment 1,” “segment 2,” “segment 3,” “additional nucleotide,” ‘CUCM1,” and “CUCM2.” In the case of “segment 1,” “segment 2,” “segment 3,” “additional nucleotide,” there is no limitation as to the specific nucleotide sequence of these segments, so any sequence could infringe them. In the case of “CUCM1” and “CUCM2” the only structural requirement is that they are cleaved in the presence of the glycosylase.
Milton et al. discloses an in vitro method of synthesizing a double stranded polynucleotide wherein a first polynucleotide strand is extended followed by a second polynucleotide strand being extended. (p. 2 lines 13-19) This method more specifically comprises steps of providing a scaffold polynucleotide, incorporating into the scaffold polynucleotide an additional blocked nucleotide, cleaving the scaffold at a cleavage site, ligating a polynucleotide to the scaffold, wherein the ligation polynucleotide contains a partner nucleotide for the newly added predetermined nucleotide, and then removing the blocking group to perform another incorporation step. (p. 3 lines 4-21, p. 4 line 24 – p. 6 line 17) The polynucleotide further comprises a single strand break in one strand and a universal nucleotide in the other. (p. 4 lines 25-27) The universal nucleotide is then cleaved in order to provide an overhanging nucleotide on the synthesis strand. (p. 5 lines 5-9) This cleavage can comprise removing the universal nucleoside, using an enzyme such as human alkyladenine DNA glycosylase, to form an abasic site which is then cleaved. (p. 15 line 25 – p. 16 line 7) Taken from the abstract, the overall scheme is pictured as follows:
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As illustrated, the scheme includes providing a scaffold, equivalent to step (a) in present claim 1, incorporating the nucleotide, cleavage at the universal nucleotide which if performed with a DNA glycosylase is equivalent to the “digesting” step b, ligation equivalent to step (d), and deprotection. While the “incorporation” step is not discussed in present claim 1, the transitional phrase “comprising” appearing in this claim indicates that it also encompasses processes comprising additional steps, such as the aforementioned incorporation step. Because the “Segment” portions of the polynucleotides recited in present claim 1 are not defined as having a particular sequence, they are infringed by whatever sequence is present in the scaffold and ligation strands described by Milton. Regarding the CUCM1 and CUCM3 motifs recited in claim 1, this motif would be infringed by the universal base described by Milton. Additionally, a single universal base would also infringe claims 7 and 9 when x and y are 0.
Regarding claim 5, Milton et al. discloses that the oligonucleotide synthesis can be performed attached to a solid surface. (p. 75 lines 4-17) Regarding claim 6, Milton describes the attachment surface being a paramagnetic bead. (p. 76 lines 19-23) The polynucleotides can further be attached to the surface reversibly by streptavidin. (p. 78 lines 14-17)
Regarding claim 10, since the (N) nucleotides are not specifically defined, a total of four nucleotides flanking the universal base could be designated as part of “CUCM1”, thereby infringing this limitation. Regarding claims 22 and 23, Milton describes the primer and support strands as being attached to one another by a hairpin, which would result in them both being ligated to the synthesis strand simultaneously. (p. 122 lines 16-19)
For these reasons Milton et al. anticipates the present claims.
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.
Claims 11-18 are rejected under 35 U.S.C. 103 as being unpatentable over Milton et al. (PCT international publication WO2018/134616, Reference included with PTO-1449)
The disclosure of Milton et al. is discussed above. Milton et al. does not specifically disclose methods wherein the oligonucleotide segments have the specific lengths recited in present claims 11-18. However, Milton et al. generally describes the primer strand as having a wide variety of potential lengths, for example 15 bases or more, or 30 bases or more. (p. 122 lines 3-7) Furthermore the polynucleotide being synthesized by Milton’s method can have a wide variety of lengths, for example 10-100, 10-200, or 10-300 nucleotides. (p. 70 lines 8-18)
It would have been obvious to one of ordinary skill in the art at the time of the invention to perform the synthesis method described by Milton et al. wherein the various segments of the polynucleotides have lengths falling within the ranges recited in claims 11-18. On of ordinary skill in the art would have found it to be obvious to adjust the lengths of the polynucleotides based on the specific target polynucleotide being synthesized.
Therefore the invention taken as a whole is prima facie obvious.
Claims 11-18 are rejected under 35 U.S.C. 103 as being unpatentable over Jacobson et al. (PCT international publication WO2011/150168, Reference included with PTO-1449)
The disclosure of Jacobson et al. is discussed above. Jacobson et al. does not specifically disclose methods wherein the oligonucleotide segments have the specific lengths recited in present claims 11-18. However, Jacobson et al. generally discloses that the polynucleotide being can have a wide variety of lengths, for example 10-300 nucleotides. (p. 10 lines 28)
It would have been obvious to one of ordinary skill in the art at the time of the invention to perform the synthesis method described by Jacobson et al. wherein the various segments of the polynucleotides have lengths falling within the ranges recited in claims 11-18. On of ordinary skill in the art would have found it to be obvious to adjust the lengths of the polynucleotides based on the specific target polynucleotide being synthesized.
Therefore the invention taken as a whole is prima facie obvious.
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Jacobson as applied to claims 1, 2, 7, 9, and 10-18 above, and further in view of Wang et al. (Reference included with PTO-892)
The disclosure of Jacobson et al. is discussed above. Jacobson et al. does not disclose an embodiment wherein the fluorescent label is FAM. However, Wang discloses fluorescent labeling of DNA with the fluorescent group FAM. (abstract) It would therefore have been obvious to one of ordinary skill in the art at the time of the invention to use FAM as the fluorescent label in the method described by Jacobson et al. One of ordinary skill in the art would have seen Jacobson’s disclosure as indicating that a wide variety of fluorescent labels can be used, and would have looked to other instances of such labels in the art.
Therefore the invention taken as a whole is prima facie obvious.
Conclusion
Claims 1-7, 9-18, 22, and 23 are rejected. Claims 8 and 19-21 are objected to for depending from a rejected base claim but would be allowable if rewritten in independent form incorporating all the limitations of the rejected base claim and any intervening claims.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ANDREA OLSON whose telephone number is (571)272-9051. The examiner can normally be reached M-F 6am-3:00pm.
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/ANDREA OLSON/Primary Examiner, Art Unit 1693 6/12/2026
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