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 .
Information Disclosure Statement
No IDS has been filed to date of the instant Office communication.
Drawings
The drawings received on January 11, 2023 are objected to because some of the figure texts are too small and unclear to be legible (see Figure 1 and 2 and their associated texts). Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
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 7 is 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 7 is indefinite for reciting the trademark 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, 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.
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, and 5-7 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Wakimoto et al. (Current Protocols in Molecular Biology, July 2014, Suppl. 107, pages 2.15.1-2.15.9).
With regard to claim 1, Wakimoto et al. teach a method depicted by the below figure (from Fig. 1):
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As seen, the method comprises the steps of: (a) providing a dsDNA template (“[i]isolation of ssDNA from double-stranded DNA (dsDNA) is a critical step”, page 2.15.1, 1st column; “1 ml 100 nM DNA template”, page 2.15.2); (b) selecting either the (+)-strand or the (-) strand of the dsDNA as the target ssDNA1; (c) providing forward and reverse primers, wherein the target ssDNA is the (-) strand and biotin is labeled to the forward primer; (d) performing a polymerase chain reaction (see PCR reaction above, also page 2.15.3); (e) once the PCR is terminated, purifying the biotinylated dsDNA fragments (see purification with spin column step in 2.15.3; “[p]urified PCR product (from Basic Protocol 1 or Alternate Protocol), page 2.15.5); and (f) separating the target ssDNA from the biotinylated DNA, wherein separating comprises (i) immobilizing the biotinylated dsDNA onto a surface (see bead capture of the biontinylated dsDNA above; also, page 2.15.5, “Capture biotinylated DNA”); (ii) adding a basic solution to the immobilized biotinylated DNA to form a dsDNA solution (“Melt Solution (125 mM NaOH)”, page 2.15.7; also “[a]dd 50 ml freshly prepared melt solution to the beads”, pages 2.15.5); (iii) neutralizing the dsDNA-exposed solution (“transfer the solution containing ssDNA fragments to the tubes containing 500 ml of neutralization solution”, page 2.15.6); and (iv) precipitating the target DNA (“[a]dd 3 ml … glycogen to the neutralized solution containing the ssDNA fragments … add an equal volume of isopropanol, mix, and centrifuge …”, this results in precipitation of the ssDNA into a pellet, see page 2.15.6), wherein ssDNA is produced.
With regard to claim 2, the artisans teach the use of dsDNA that is between 50 base pairs to 8 kilobases in length (“Pippin Prep is designed for the extraction of dsDNA between 50 base pairs (bp) and 8 kilobases (kb)”, page 2.15.2).
With regard to claim 5, the PCR is cleaned up in a purification process, and the PCR contained dNTP, primers, and a DNA polymerase (see Figure 1 above).
With regard to claim 6, the purification comprises centrifugation (see purification method on page 2.15.3).
With regard to claim 7, the surface comprises streptavidin coupled Dynabeads (see page 2.15.5, Materials, “Dynabeads® M-270 streptavidin”).
Therefore, the invention as claimed is anticipated by Wakimoto et al.
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 3 and 4 are rejected under 35 U.S.C. 103 as being unpatentable over Wakimoto et al. (Current Protocols in Molecular Biology, July 2014, Suppl. 107, pages 2.15.1-2.15.9) in view of Petri et al., BioTechniques, 2014, pages 269-270 and 272-273).
The teachings of Wakimoto et al. have already been discussed above.
While Wakimoto et al. discuss the well-known means of sequencing ssDNA sequences, the artisans do not explicitly teach that the sequenced ssDNA contains flanking ITR or does not comprise flanking ITR regions
Petri et al. teach a well-known practice in the art of sequencing nucleic acids which comprise ITR flanked regions (see Abstract).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Wakimoto et al. with the teachings of Petri et al., thereby arriving at the invention as claimed for the following reasons.
In KSR, the Supreme Court particularly emphasized “the need for caution in granting a patent based on the combination of elements found in the prior art,” Id. at 415, 82 USPQ2d at 1395, and discussed circumstances in which a patent might be determined to be obvious. Importantly, the Supreme Court reaffirmed principles based on its precedent that “[t]he combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results.” Id. at 415-16, 82 USPQ2d at 1395. The Supreme Court stated that there are “[t]hree cases decided after Graham [that] illustrate this doctrine.” Id. at 416, 82 USPQ2d at 1395. (1) “In United States v. Adams, . . . [t]he Court recognized that when a patent claims a structure already known in the prior art that is altered by the mere substitution of one element for another known in the field, the combination must do more than yield a predictable result.”
Similarly, taking the teachings of Wakimoto et al. and generating a ssDNA strand for sequencing that comprises sequences commonly sequenced in the art, as evidenced by Petri et al., such as those flanked by ITR or not flanked by ITR would have yielded no more than a predictable outcome of yielding a sequencing template.
For these reasons, the invention as claimed is deemed prima facie obvious over the cited references.
Claims 8-10 are rejected under 35 U.S.C. 103 as being unpatentable over Wakimoto et al. (Current Protocols in Molecular Biology, July 2014, Suppl. 107, pages 2.15.1-2.15.9).
The teachings of Wakimoto et al. have already been discussed above.
While Wakimoto et al. teach the use of NaOH to denature the non-biotinylated strand from the biotinylated complementary strand bound to a streptavidin-coated magnetic bead, the artisans do not explicitly teach that 1M NaOH of 1mL is employed or that equimolar acetic acid is used for the neutralization process (claims 8 and 9). As well, Wakimoto et al. teach an alcohol precipitation using isopropanol and not ethanol (claim 10).
However, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed inventio to combine the teachings of Wakimoto et al. with commonly employed techniques in the art based on conventional knowledge, thereby arriving at the invention as claimed for the following reasons.
As to the use of ethanol instead of isopropanol for precipitation, the use of alcohol for eluted DNA strands have been well-established in the art including propanol or ethanol. Therefore, one of ordinary skill in the art would have expected the same predictable outcome of adopting other means of precipitating the ssDNA from solution which have been employed in the art as an alternative precipitating agent, such as ethanol, rendering the claim obvious.
With regard to claims 8 and 9 directed to the different concentrations of NaOH and acetic acid, the Office contends that the identification of optimal condition of prior art teachings, when known to be affect an outcome is deemed obvious as being result-effective variable.
In In re Antonie, 559 F.2d 618, 195 USPQ 6 (CCPA 1977), the CCPA held that a particular parameter must first be recognized as a result-effective variable, i.e., a variable which achieves a recognized result, before the determination of the optimum or workable ranges of said variable might be characterized as routine experimentation, because “obvious to try” is not a valid rationale for an obviousness finding.
Because Wakimoto et al. teaches that NaOH concentration employed and its amount has to do with denaturing the ssDNA from its complementary biotinylated DNA strand for purification, one of ordinary skill in the art would have been capable of performing routine titrations to identify which concentration of NaOH and its amount worked optimally to isolate the desired ssDNA (i.e., result-effective variable). In the similar fashion one of ordinary skill in the art would have been motivated to neutralize the same amount of base in the solution by use of an acid when precipitating the purified ssDNA.
Therefore, the invention as claimed is deemed prima facie obvious over the cited references.
Claims 11-15 are rejected under 35 U.S.C. 103 as being unpatentable over Wakimoto et al. (Current Protocols in Molecular Biology, July 2014, Suppl. 107, pages 2.15.1-2.15.9) in view of KR 19990021950A (published March 1999, herein “Korean Patent”, using Google Machine Translation).
The teachings of Wakimoto et al. have already been discussed above.
While Wakimoto et al. teach the use of a biotinylated primer in their method of PCR, the artisans do not explicitly teach that the biotin is separated from the primer via use of a spacer molecule (claim 11), such spacers being those defined by claims 12-15).
Korean Patent teaches a well-known concept of utilizing a spacer molecule between a biotin and a primer in a PCR reaction:
“the biotin molecule is linked to the 5’ end of the modified primer. Biotin is attached to the 5’ end of the primer through an extended primer arm providing a reduction in steric hindrance …” (page 29, bottom paragraph)
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Wakimoto et al. with the teachings of Korean Patent and means known and available in the art, thereby arriving at the invention as claimed for the following reasons.
The motivation to do so is explicitly provided by Korean Patent wherein one of ordinary skill in the art would have recognized the benefit of utilizing a spacer molecule between the 5’ biotin and the primer employed by Wakimoto et al. so as to prevent the steric hindrance from negatively affecting the PCR reaction of Wakimoto et al.
As to utilizing other prior art known spacers such as the use of carbon atom spacers, ethylene glycol unit spacers and phosphosoramidites, their use would have resulted in the yielding of the same predictable outcome of providing a desired separation between the biotin and primer in the biotinylated primer of Wakimoto et al., rendering the invention as claimed prima facie obvious. In KSR, the Supreme Court particularly emphasized “the need for caution in granting a patent based on the combination of elements found in the prior art,” Id. at 415, 82 USPQ2d at 1395, and discussed circumstances in which a patent might be determined to be obvious. Importantly, the Supreme Court reaffirmed principles based on its precedent that “[t]he combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results.” Id. at 415-16, 82 USPQ2d at 1395. The Supreme Court stated that there are “[t]hree cases decided after Graham [that] illustrate this doctrine.” Id. at 416, 82 USPQ2d at 1395. (1) “In United States v. Adams, . . . [t]he Court recognized that when a patent claims a structure already known in the prior art that is altered by the mere substitution of one element for another known in the field, the combination must do more than yield a predictable result.”
Conclusion
No claims are allowed.
Inquiries
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to Young J. Kim whose telephone number is (571) 272-0785. The Examiner can best be reached from 7:30 a.m. to 4:00 p.m (M-F). The Examiner can also be reached via e-mail to Young.Kim@uspto.gov. However, the office cannot guarantee security through the e-mail system nor should official papers be transmitted through this route.
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner's supervisor, Gary Benzion, can be reached at (571) 272-0782.
Papers related to this application may be submitted to Art Unit 1681 by facsimile transmission. The faxing of such papers must conform with the notice published in the Official Gazette, 1156 OG 61 (November 16, 1993) and 1157 OG 94 (December 28, 1993) (see 37 CFR 1.6(d)). NOTE: If applicant does submit a paper by FAX, the original copy should be retained by applicant or applicant’s representative. NO DUPLICATE COPIES SHOULD BE SUBMITTED, so as to avoid the processing of duplicate papers in the Office. All official documents must be sent to the Official Tech Center Fax number: (571) 273-8300. Any inquiry of a general nature or relating to the status of this application should be directed to the Group receptionist whose telephone number is (571) 272-1600.
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/YOUNG J KIM/Primary Examiner
Art Unit 1637 July 26, 2025
/YJK/
1 Based on the present Figure, the target strand is the (-) strand and the forward primer is biotinylated.