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 .
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
Status of Claims
Claims 13 and 47-52 are pending and under examination.
Withdrawn Rejection
In view of the amendments and new claims, the 35 U.S.C. 103 rejection over Jungmann, Archer and Diehl is hereby withdrawn.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 13 and 47-52 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a new matter rejection.
The amendment to claim 13 recites “wherein each unique MTAB-DM is conjugated to different docking strands”, which implies that each unique MTAB-DM is conjugated to at least two different docking strands. Applicant has not provided specific passages from the specification to the recited limitations having each MTAB-DM conjugating two different docking strands for the imaging method. Examiner was not able to find support for the imaging method containing a single MTAB-DM that conjugates two different docking strands.
For the reasons above, the specification fails to provide direction or blaze marks to the process of exchanging imaging of targets with each unique MTAB-DM containing different docking strands.
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 13 and 47-52 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 13 recites that “each unique MTAB-DM is conjugated to different docking strands” and later in the claim it recites that “wherein the first and second antibody are distinguished by at least the docking strand” implies that each antibody has a single docking strand. Additionally, the claim only recites contacting the sample with labeled imager strands, which implies that all the imager strands may be the same strand with different docking strands? Thus, it is unclear to the metes and bounds if whether each MTAB-DM has different docking strands or a single docking strand because the imager strands are the same. Note that the recitation of “differing imager strands” is interpreted as having different fluorophores to the imager strand.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 13 and 47-52 are rejected under 35 U.S.C. 103 as being unpatentable over Jungmann et al. (WO2015017586A1, published 02/5/2015, see 892 dated 01/16/2026) in view of Archer et al. (US20030073149A1, published 04/17/2003, IDS submitted on 06/08/2022, cite no. 1).
With respect to claim 13, Jungmann teaches compositions for imaging at high spatial resolution of targets (see abstract). Fig. 2 of Jungmann shows a composition for detecting a plurality of targets in a sample, the composition comprising: at least a first target recognizing antibody and a second target recognizing antibody, wherein the first antibody is conjugated to a first single stranded nucleic acid docking strand. Fig. 2 also shows a second antibody conjugated to a second single stranded nucleic acid docking strand and which have complementarity to an imager strand or an intermediate moiety wherein the intermediate moiety has a first domain that hybridizes to the docking strand and a second domain that hybridizes to an imager strand. Jungmann further teaches a method that can detect a plurality of targets (e.g., with each docking strand-imager strand pair corresponding to one target) and select at least 200 orthogonal different sequences to be used in these multiplexing methods (see pg. 3, lines 13-25). Jungmann teaches at least one protein-nucleic acid conjugate is bound to a target and at least one complementary labeled, optionally fluorescently, imager strand that is transiently bound to (or is capable of transiently binding to) the at least one protein-nucleic acid conjugate (see pg. 4, lines 20-27). Table 6 shows a plurality of imager strands for assaying. Jungmann further teaches contacting target species with different docking strands domain sequence and different lengths of those sequences (see pg. 37, lines 22-25 and Table 1). Jungmann teaches quenching in the assay (see pg. 2, lines 1-3). Fig. 2 shows a multiplexed super-resolution imaging of intra-cellular components in fixed cells was achieved by linking docking strands to antibodies (also see Example 1, pg. 64). Fig. 3 demonstrate two spectrally distinct species of imager strands are introduced at the same time: one species is labeled with Cy3b and is complementary to the docking strand that is linked to the mitochondrial specific and the other species is labeled with ATTO0655 and is complementary to the docking strand that is linked to the microtubule specific antibody (also see pg. 33, lines3-17). Jungmann teaches spectrally distinct molecules refer to molecules with labels (e.g., fluorophores) of different spectral signal or wavelength, and for example, an imager strand labeled with a Cy2 fluorophore emits a signal or wavelength of light of about 510 nm, while an imager strand labeled with a Cy5 fluorophore emits a signal at a wavelength of about 670 nm (see pg. 30, lines 4-10). Jungmann teaches the imager strand that is complementary to and transiently binds to the docking strand of the first protein-nucleic acid conjugate, imaging the sample to obtain a first image, optionally using time-lapsed imaging, removing the first labeled imager strand, and the sample with at least one other labeled image strand that is complementary to and transiently binds to the docking strand of the at least other protein-nucleic acid conjugate, and imaging the sample to obtain at least one other image with using time-lapsed imaging (see pg. 8, lines 5-12).
Jungmann does not teach the unique monovalent tight antibody binders conjugating to docking strands (claim 13) wherein monovalent tight antibody binder is Protein A, G, A/G, or L or monovalent antibody fragment.
Archer teaches novel immunolabeling complexes and certain components of such complexes and teaches novel labeling proteins monovalent antibody fragments and the fragments are labeled Fab fragments of an anti-Fc antibody (see abstract and Fig. 1). Archer teaches that in Fig. 2 it represents biotinylated goat Fab anti-mouse Fc (see para. [0014]). Archer teaches that a particular advantage of the current labeling of target binding antibodies is that it provides for a novel method to directly label the antibodies in any solution containing primary amines or non-antibody proteins (see paras. [0060] and [0090]). Archer teaches the compositions include isolated immunolabeling complexes and isolated monovalent labeling proteins and the labels that are attached to the labeling proteins are directly detectable moieties which directly detectable moieties are optionally the same or different (see para. [0078]). Archer teaches Protein A means proteins comprising more natural IgG-binding domains of protein A, hybrids of the natural IgG-binding domains, and mutants thereof wherein the variant retains the capability of binding IgG or fragments (see para. [0049]). Archer teaches labeling protein with Protein A, Protein G or Protein L and monovalent Fab fragments specific for Fc portion are used from monoclonal antibodies (also see para. [0057]).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to have modified the assay compositions as taught by Jungmann with a monovalent antibody fragment or Protein A, G or L as taught by Archer because Archer teaches that the advantage of labeling with monovalent antibody fragments or Protein A, G or L is that it provides a direct labeling to the primary antibody with the knowledge that these elements are recognized in the art to bind to Fc region of antibodies. Therefore, it would have been obvious to the person to have simply used monovalent antibody fragment or Protein A, G or L labeling because the primary antibodies do not need to be modified with linkers such as biotin for streptavidin binding, as these elements of Archer recognize Fc region which is not specific to target binding regions.
The person would have a reasonable expectation of success in using monovalent antibody fragments to attach to the primary antibody of Jungmann because it has been well recognized to perform the assay with IgG antibody which contains an Fc region and Archer recognizes labeling with said fragments to the Fc region of the antibody for assay detection.
With respect to claims 47 and 48, Archer teaches the monovalent tight antibody binder is Protein A, Protein G or Protein L or monovalent Fab fragments specific for Fc portion are used from monoclonal antibodies (also see para. [0057]).
With respect to claim 49, Jungmann teaches in Fig. 2 the structure of an IgG antibody. However, Jungmann does not explicitly recite the phrase IgG antibody. Archer teaches detecting IgG (see para. [0014]). It would have been obvious to have used IgG for detection and reasonably expected success because the monovalent antibody fragment or Protein A, G or L binds to Fc region of IgG.
With respect to claim 50, Archer teaches labeling protein is a monovalent Fab fragment specific for Fc portion are used from monoclonal antibodies (also see para. [0057]), which would comprise scFv.
With respect to claim 51, Archer teaches the monovalent tight antibody binder is Protein A, Protein G or Protein L or monovalent Fab fragments specific for Fc portion are used from monoclonal antibodies (also see para. [0057]).
With respect to claim 52, Jungmann teaches using fixed HeLa cells (see pg. 21, lines 30-34).
Response to Arguments
Applicant's arguments filed 04/16/2026 have been fully considered. Although the obviousness rejection above has been modified in view of the amendments but the arguments are not persuasive.
Applicant argues on page 5 of the Remarks that neither of the cited references disclosed, teach or reasonably suggest “unique monovalent tight antibody binder-docking moiety (MTAB-DM”, wherein each unique MTAB-DM is conjugated to different docking strands and labeled imager strands, wherein the labeled imager strands comprise a portion that hybridizes to the docking strand and a fluorescent label.
The arguments are not found persuasive because, as stated above, the only difference between Jungmann and the claimed invention is that Jungmann does not teach using a monovalent tight antibody binder. As stated above, monovalent antibody fragments or Protein A, G or L has been recognized in the art for binding to Fc region of antibodies, which does not affect the target binding affinity of the antibody. Therefore, it would have been obvious to have simply used monovalent antibody fragment or Protein A, G or L labeling because the primary antibodies do not need to be modified with linkers such as biotin for streptavidin binding, as these elements of Archer recognize Fc region which is not specific to target binding regions.
Conclusion
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/N.P.N/Examiner, Art Unit 1678
/SHAFIQUL HAQ/Primary Examiner, Art Unit 1678
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