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 the reply filed on 7/21/2025 is acknowledged. The traversal is on the ground(s) that there would be no burden to search the groups together. This is not found persuasive because the search of the product claims would require different keywords and concepts.
The requirement is still deemed proper and is therefore made FINAL.
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 4 and 8 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 4 depends from itself. The metes and bounds of the claim are unclear.
Claim 8 recites a group of alternatives that comprises “but is not limited to” the recited sample types. MPEP § 2173.05(h)(I), “If a Markush grouping requires a material selected from an open list of alternatives … e.g., … selected from the group ‘comprising’ [as in the instant case] … the claim should generally be rejected under 35 U.S.C. § 112(b) as indefinite because it is unclear what other alternatives are intended to be encompassed by the claim.” As noted above, claim 8 impermissibly uses open-ended “comprising” language. Accordingly, it’s unclear which Markush members (in addition to the ones expressly listed) should be included within the scope of these claims consistent with MPEP § 2173.05(h)(I).
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) 1-3, 5-8 and 14-15 is/are rejected under 35 U.S.C. 103 as being unpatentable over Italia et al. (WO 2021/034971) in view of Nong et al. (Nature Protocols Vol. 8, No. 6, pages 1234-1248).
Italia et al. claims priority to US 62/888597, filed 8/19/2019. Portions of the WO reference that are relied upon in this rejection have basis in the provisional application.
Italia et al. teach a method of detecting one or more analytes in a sample, the method comprising:
forming a first antibody-analyte-second antibody complex by incubating the first antibody-analyte complex with (a) at least one portion of a second antibody conjugated with a nucleic acid fragment comprising an exposed 3' hydroxyl group and (b) at least one portion of another second antibody conjugated with a nucleic acid fragment comprising an exposed 5' phosphate group (See Figure 1 showing two antibodies coupled to oligonucleotides);
ligating the nucleic acid fragment comprising the exposed 3' hydroxyl group and the nucleic acid fragment comprising the exposed 5' phosphate group (See Figure 1 showing ligating the two probes);
separating the ligated nucleic acid fragments from the first antibody-analyte- second antibody complex (See Figure 1, “release “U” digestion which illustrates digesting uracils in the oligonucleotides conjugated to the antibodies);
amplifying the ligated nucleic acid fragments (Figure 1(F) amplification); and detecting the one or more analytes present in the sample based on the amplified nucleic acid fragments (Figure 1(F), qPCR probe).
With regard to claim 5, Italia teaches amplifying that comprises qPCR.
Italia et al. does not teach step (a) as claimed.
Italia et al. does not teach that the probes have exposed ends as required, nor does Italia teach how the ligation proceeds.
Italia et al. does not teach a pre-amplification prior to qPCR.
Italia et al. is silent as to the sample type.
Nong teaches the development of a generally useful solid-phase PLA protocol based on spherical magnetic microparticles for robust and highly sensitive detection. The method is very similar to the method taught by Italia et al., including the use of antibodies conjugated to antibodies, ligation of proximal oligonucleotides and PCR amplification (Figure 1). The method taught by Nong includes a step of introducing the sample to a surface bound to one or more first antibodies, wherein the surface is bound to at least one portion of each first antibody to form a first antibody-analyte complex, that is Nong teaches capture of the target using a surface bound first antibody followed by subsequent exposure to second and third antibodies (Figure 1).
Furthermore, Nong teaches ligation of the two antibody conjugated oligonucleotides by employing a ligase enzyme. Nong teaches that the oligonucleotides that participate in the ligation reaction via their 5’ end must be phosphorylated (p. 1237, 2nd column), and it is inherent that the opposite participating oligonucleotide must have an exposed 3’ hydroxyl because that is how enzymatic ligation proceeds.
Nong teaches that in multiplex amplification a preamplification occurs before final detection (Figure 2).
Nong teaches detection of single or multiple proteins in blood, plasma, cerebrospinal fluid or in tissue lysates by requiring recognition of target molecules by sets of three antibodies (p. 1235).
It would have been obvious to one having ordinary skill in the art to have modified the method taught by Italia so as to have included a first step of target capture using a surface bound antibody, to have included a preamplification step in to facilitate a multiplex assay and to assay blood, plasma, or cerebrospinal fluid. One would have been motivated do so because Nong teaches that the SP-PLA offers “highly specific and sensitive detection of single or multiple proteins in blood, plasma, cerebrospinal fluid or in tissue lysates by requiring recognition of target molecules by sets of three antibodies” (p. 1235). Furthermore, it would have been obvious to have employed the enzymatic ligation taught by Nong in order to provide the predictable result of ligating the proximity probe in preparation for readout.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Hammond (2014; cited in IDS 10/22/2023) teaches a solid phase proximity ligation assay wherein second and third antibodies are the same clonal antibody (See figure 1).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Juliet Switzer whose telephone number is (571)272-0753. The examiner can normally be reached Monday to Thursday, 8:00 AM-3:30 PM.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Winston Shen can be reached at (571)-272-3157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
Juliet Switzer
Primary Examiner
Art Unit 1682
/JULIET C SWITZER/ Primary Examiner, Art Unit 1682
Prosecution Insights