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 without traverse of Group I in the reply filed on March 30, 2026 is acknowledged.
Invention encompassed by claims 17 and 18, now canceled, is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 without traverse in the reply filed on March 30, 2026.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The IDS received on September 29, 2023; November 16, 2023; February 27, 2025; and July 15, 2025 are proper and are being considered by the Examiner.
Drawings
New corrected drawings in compliance with 37 CFR 1.121(d) are required in this application because the Figures are poor in quality and their texts are not clearly legible. For example, Figures 1-1 and 1-2 contain texts which are not clearly legible due to poor quality. Applicant is advised to employ the services of a competent patent draftsperson outside the Office, as the U.S. Patent and Trademark Office no longer prepares new drawings. The corrected drawings are required in reply to the Office action to avoid abandonment of the application. The requirement for corrected 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.
Claims 1, 7-14 and 20 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 1 is indefinite for reciting an end parenthesis without an opening parenthesis (see the phrase ending with “antibody-tracer nucleic acid complex” that ends with a parenthesis but no previous parenthesis is present.
In addition, the Office suggests removing the phrase “also referred to as ‘capture nucleic acid-anti-nucleic acid therapeutics antibody-tracer nucleic acid complex’)”. This phrase can be better replaced with the term “a first complex” as it is previously described as a complex that is formed from the three elements (i.e., capture nucleic acid, nucleic acid therapeutic antibody, and tracer nucleic acid). Presently employed term is long and does not serve to render the claim concise.
Claim 7 recites the term, “anti-drug antibodies”. There is no longer a proper antecedent basis for this limitation as claim 1 has been amended to remove this term, now replaced with the term, “anti-nucleic acid therapeutics antibody”. The claim has been construed to be referring to this new term.
Claims 20 and 21 recite an element which is an admitted trademark (see phrase, “ENA (registered trademark)”. Usage of a trademark in a claim renders the claim indefinite because a trademark identifies the source of the good and not the good itself. For example, Coke® has maintained its tradename over decades while changing its formulation.
The Office suggest the removal of the trademarked elements (if additional ones are recited) or replacing the element with a generic description.
Claims 7-14 and 20 are indefinite by way of their dependency on claim 1.
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.
Claim 12 is 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 12 depends from claim 11.
Claim 11 explicitly requires a first step of bringing the sample and the capture nucleic acid into contact with each other that forms a first complex (when anti-nucleic acid therapeutics antibody is present) and a second step of bringing a product of the first step and the tracer nucleic acid into contact with each other, forming a second complex.
Claim 12 recites that the first complex and second complex forming steps are performed simultaneously. Because claim 11 explicitly require that these two steps are performed separately, a dependent claim cannot now require them to be occurred simultaneously, because when something occurs simultaneously, a first and second steps no longer occur in isolation or in succession. Consequently, claim 12 is outside of the scope established by parent claim 11.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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 1, 4, 6-14, 16, 20, and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Kozlov et al. (WO 2015/070037 A2, published May 2015) in view of Zhang et al. (Journal of Controlled Release, December 2016, vol. 244, pages 184-193).
With regard to claims 1, 4, and 11, Kozlov et al. teach a method of detecting an antibody depicted by the below-reproduced figure (from Fig. 4):
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As seen, the method disclosed by Kozlov et al. teach a method comprising: (a) a step of bringing a sample, a capture nucleic acid (see DNA on the top-left corner); and a tracer nucleic acid (see DNA on the bottom-right corner) into to form a complex of the capture nucleic acid, the antibody, and the tracer nucleic acid (see complex after step (ii), wherein the capture nucleic acid and the tracer nucleic acid each has an epitope to which the antibody binds (see wherein antibody binds to the epitopes on the top-left corner and bottom-right corner DNAs); and (b) a step of detecting the capture nucleic acid-antibody-tracer nucleic acid complex (see step (iii), wherein the complex formed is detected, also “method further comprises analyzing the first and/or second polynucleotides engaged via the first and second engaging sequences, wherein the analyzing step indicates the presence, absence, and/or amount of the antibody or antigen binding fragment thereof in the sample).
With regard to claim 8, the first and second epitope to which the antibody binds are the same (“the first and second epitopes for specific binding of the antibody or antigen binding fragments thereof can be the same”, section [0014]).
With regard to claim 12, the first and second complex forming steps are performed simultaneously (“[i]n certain other aspects, the first and second polypeptide-polynucleotide conjugates [i.e., the capture and the tracer nucleic acids] are pre-loaded on the support substantially simultaneously …” section [00135]).
With regard to claims 13 and 14, one or both of the capture nucleic acid and tracer nucleic acid are modified with LNA (“the polynucleotide portion of a polypeptide-polynucleotide conjugate can be polynucleotide of any suitable length … can be single-, double, and/or triple stranded DNA, RNA, PNA, or LNA”, section [0118]).
With regard to claim 16, the sample is biological sample, such as blood (“samples include, but are not limited to body fluids, such as blood”, section [0073]).
Kozlov et al. do not explicitly teach that the antibody is an anti-nucleic acid therapeutic antibody (claims 1 and 4, in-part), wherein two or more Ig classes of anti-nucleic acid therapeutic antibodies are detected by one measurement when IgG, IgM, IgD, IgE, or IgA class antibody is present in the sample (claim 7).
Consequently, Kozlov et al. do not teach that the epitope to which the anti-nucleic acid therapeutics antibody binds is those listed in claims 20 and 22.
Kozlov et al. while explicitly teaching washing of the unbound complex, do not particular teach that the anti-nucleic acid therapeutic antibody bound to capture nucleic acid is first washed (claim 6).
While Kozlov et al. teach that the capture and tracer nucleic acids can be of any length (see section [0118]), the artisans do not particularly teach that they are of the same length or differ by 1 to 60 bases (or mers) (claim 9), longer by 10- to 50-mers (claim 1).
Zhang et al. teach the problems that exists in body’s generation of anti-drug antibody in therapies:
“several reports correlated the generation of anti-PEG Abs with loss of therapeutic efficacy and there has been an increase of reports of adverse effects after repeated administrations.” (page 184, 2nd column, bottom paragraph to page 185, 1st column)
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 Kozlov et al. with the teachings of Zhang et al., thereby arriving at the invention as claimed for the following reasons.
As discussed above, Kozlov et al. teach a method of detecting antibody that is generated in a sample of a subject, wherein the detection is mediated by the capture of the antibody in the sample with a first nucleic acid probe that comprises an epitope of said antibody (i.e., capture probe) and a second nucleic acid probe that comprises an epitope of the same antibody (i.e., tracer probe), wherein the complex formed is isolated from the sample and the resulting product, detected.
While Kozolov et al. did not explicitly list every type of assays for which the generated antibody can be detected, one of ordinary skill in the art would have been motivated to apply the teachings of Kozlov et al. for solving the issues raised by Zhang et al. in the area of therapy wherein the subject produces antibodies against a component of the drug, such as PEG which is used in drug-mediated therapy:
“structurally complex biomacromolecules usually face great challenges including instability, inadequate circulation half-life and immunogenicity. A short half-life limits therapeutic efficacy and requires a frequent administration regimen. Immune responses against many biological drugs not only result in accelerated blood clearance during chronic use, but also threatens patients’ lives with adverse effects including anaphylaxis and infusion reactions” (page 184, 1st column, 1st paragraph)
“The most successful strategy thus far to overcome these shortcomings is the conjugation of polyethylene glycol (PEG) to these biomacromolecules, a process known as PEGylation” (page 184, 1st column, 2nd paragraph)
“several reports correlated the generation of anti-PEG Abs with loss of therapeutic efficacy and there has been an increase of reports of adverse effects after repeated administrations.” (page 184, 2nd column, bottom paragraph to page 185, 1st column)
“Based on the clinical findings … it would be beneficial to screen and monitor both pre-existing and induced anti-PEG Abs during the treatment of PEGylated therapeutics” (page 187, 2nd column, 2nd paragraph)
With this motivation one of ordinary skill in the art would have been motivated design the oligonucleotide probe-epitope conjugates of Kozlov et al. to arrive at epitopes which bind to anti-PEG Abs, such as IgM, IgG (see page 187, 2nd column, 4th paragraph), allowing the artisan to assay for the anti-drug therapy antibody generated.
While it is noted that the anti-drug therapy discussed by Zhang et al. is related to PEGylated protein, because the antibody is generated against PEG component, application of the teachings would have been equally applicable in therapies based on nucleic acids that rely on the presence of PEGs.
With regard to the step of trapping (or isolating) the capture nucleic acid is to perform binding of the capture nucleic acid to a solid phase, and the separation and removal of the unbound capture nucleic acid is via washing the solid phase-bound capture nucleic acids, Kozlov et t al. that that the capture nucleic acid is bead bound, as well as teaching that, “following analyte capture, the support is washed under conditions that destabilize the transient complex between the first and second polypeptide-polynucleotide conjugates, retaining the polypeptide-polynucleotide conjugates engaged in the ternary complex while releasing those not engaged in the ternary complex (e.g. , those first and second polypeptide-polynucleotide conjugates interacting via the engaging sequences only, and not via specific binding to the bivalent analyte). In this case, only the polypeptide-polynucleotide conjugates specifically bound to the bivalent analyte (e.g., an antibody) in the ternary complex contribute to assay signal.”, section [00135]). Because the order of the binding and the steps of wash would have resulted in the same result of the specifically bound antibody to the both capture and tracer nucleic acids for detection, such order would have been obvious in view of yielding a predictable outcome.
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.”
As to the length of the capture and tracer nucleic acid probes employed by Kozlov et al., the artisans teach that the capture and tracer nucleic acids can be of any length (see section [0118]), and while the artisans do not particularly teach that they are of the same length or differ by 1 to 60 bases (or mers), or longer by 10- to 50-mers, doing so would have been obvious in view of utilization of sequences that yield the most optimal result as the length and base contents of the nucleic acids would have been directly related to the hybridization efficiency (i.e., result-effective).
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.
Therefore, the invention as claimed is deemed prima facie obvious over the cited references.
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, 4, 6-14, 16, and 20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 and 13-21 of copending Application No. 18/857,531 (reference application) in view of Zhang et al. (Journal of Controlled Release, December 2016, vol. 244, pages 184-193).
Although the claims at issue are not identical, they are not patentably distinct from each other for the following reasons.
With regard to instant claim 1, claims of the reference application also claims a process of detecting an “analyte,” wherein said analyte is detected by contacting: 1) a self-assembly of probes that is a signal producer, said assembly comprising an oligonucleotide that binds to the analyte, 2) analyte; and 3) a capture probe that also binds to the analyte, and detecting said complex. The resulting structure produced by the claims (claim 1) of the reference application is structurally similar to that of instant claim 1, that is a structure that is formed by contacting an analyte (i.e., antibody) that is bound to a capture probe and a tracer probe (or the self-assembly of probes).
Zhang et al. teach the problems that exists in body’s generation of anti-drug antibody in therapies:
“several reports correlated the generation of anti-PEG Abs with loss of therapeutic efficacy and there has been an increase of reports of adverse effects after repeated administrations.” (page 184, 2nd column, bottom paragraph to page 185, 1st column)
While the claims do not explicitly recite that the analyte is an antibody or an anti-nucleic acid therapeutics antibody in the sample, the application itself in totem is directed to the detection of the antibody (see Fig 1, for example), and in view of the teachings of Zhang et al. discussed above, one of ordinary skill in the art before the effective filing date of the claimed invention would have been motivated to apply the claimed method of the reference application to detect antibody generated against a component of a drug employed in a therapy, such as PEG.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
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 May 23, 2026
/YJK/
Prosecution Insights